Antiviral T cells safe, effective as off-the-shelf therapy for painful complication after stem cell transplants – News-Medical.Net

A Phase II trial led by researchers at The University of Texas MD Anderson Cancer Center found that BK virus (BKV)-specific T cells from healthy donors were safe and effective as an off-the-shelf therapy for BKV-associated hemorrhagic cystitis (BKV-HC), a painful complication common after allogeneic stem cell transplants for patients with leukemia or lymphoma. The study was published today in the Journal of Clinical Oncology.

Infusion of T cells targeting BKV resulted in rapid responses, with 67.7% of patients seeing a complete or partial improvement in symptoms after 14 days. This increased to 81.6% of patients after 28 days post-infusion. No cases of grade 3 or grade 4 graft versus host disease (GVHD) or other infusion-related toxicities occurred.

BKV-associated hemorrhagic cystitis is an incredibly painful condition that causes significant morbidity in patients and can lead to worse cancer outcomes in the long term. Unfortunately, there are no effective treatments available. We were driven to develop this therapy to provide a better option for these patients, and this has emerged as a safe and effective therapy for patients at MD Anderson based on these results."

Katy Rezvani, M.D., Ph.D., Corresponding Author, Professor of Stem Cell Transplantation and Cellular Therapy

BKV is a human polyomavirus acquired by most people in early childhood, Rezvani explained. Held in check by the immune system, BKV typically remains inactive in the cells lining the urinary tract, including the kidney, bladder and ureters.

Allogeneic stem cell transplants, in which stem cells come from a matched donor, require patients to be given therapies to suppress the immune system and prevent rejection. However, this also can trigger the BKV to begin reproducing and cause severe cystitis, which can result in hospitalization for days or weeks. An antiviral called cidofovir has been used as a treatment but is associated with significant toxicities.

Recognizing that these viral infections can profoundly impact patient recovery, Rezvani and her research team led the development of antiviral T-cell therapies with the support of the MDS and AML Moon Shot, part of the institution's Moon Shots Program, a collaborative effort to rapidly develop scientific discoveries into meaningful clinical advances that save patients' lives.

Beginning with blood samples taken from healthy donors, the research team is able to isolate T cells and grow them to specifically recognize and target a variety of antigens found on the BKV. These cells are expanded in the clinical good manufacturing practice (GMP) laboratory, under the leadership of Elizabeth J. Shpall, M.D., professor of Stem Cell Transplantation and Cellular Therapy. From each donor, the team can manufacture anywhere from 20 to 50 doses of antiviral T cells, which are stored until needed, Rezvani said.

In a previous trial published in the New England Journal of Medicine, these researchers showed that BKV-specific T cells can effectively treat infection with the JC virus, a genetically similar polyomavirus that causes progressive multifocal leukoencephalopathy (PML), a rare and often fatal brain infection.

The current trial enrolled a total of 59 MD Anderson patients experiencing BKV-HC following an allogeneic stem cell transplant. Patients had a median age of 47 and were being treated for a variety of hematological conditions, the most common being acute myeloid leukemia. Women accounted for 40.7% of participants and men for 59.3%. Among trial participants, 55.9% (33) were white, 18.6% (11) were Hispanic, 15.3% (9) were African-American, 6.8% (4) were Middle-Eastern and 3.4% (2) were Asian.

Patients received a single infusion of partially human leukocyte antigen (HLA)-matched T cells, with the option to receive additional infusions every two weeks, if needed.

Following infusion, the researchers did not observe any side effects that were likely attributed to the antiviral T cells. No infusion-related toxicities, low blood-cell counts or graft failures were found. Several patients developed delayed cases of low-grade GVHD in the weeks and months following treatment, which were well within the expected rates of GVHD for these patients early after allogeneic stem cell transplant, Rezvani explained.

The median time for patients to have a partial response was 14 days, and the median time to complete response was 21 days. The estimated probability of achieving a complete response was nearly 70% by day 45, indicating continuous activity of the infused cells. Responses were durable and no patients saw their symptoms return after a previously achieved response.

After studying participants on the trial, the researchers determined that expansion of the infused T was positively correlated with patient responses.

"We are extremely encouraged by the safety of this treatment and the rapid responses we've seen in the majority of patients," Rezvani said. "Because this approach is so safe, we've been able to offer this treatment as an outpatient procedure as soon as patients begin developing symptoms. This has been life-changing for the patients we've been able to treat so far."

In the future, the researchers aim to validate these findings in a multi-institutional study and bring this treatment option to many more patients in need.

A full list of collaborating authors and their disclosures can be found with the full paper here. In addition to the Moon Shots Program, the research was supported by the National Institutes of Health (R01CA211044-05, CA016672).

Source:

Journal reference:

Olson, Z., et al. (2021) Third-Party BK Virus-Specific Cytotoxic T Lymphocyte Therapy for Hemorrhagic Cystitis Following Allotransplantation. Journal of Clinical Oncology. doi.org/10.1200/JCO.20.02608.

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Antiviral T cells safe, effective as off-the-shelf therapy for painful complication after stem cell transplants - News-Medical.Net

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Mesoblast says its stem cell treatment saved lives of severely ill COVID patients – Stockhead

Mesoblast (ASX:MSB) has released more data from its halted COVID-19 trial, saying its stem cell treatment apparently significantly reduced mortality in severely ill younger patients but the controversial biotech isnt sure it will seek an emergency use authorisation for it.

Mesoblasts remestemcel-L infusion reduced death by 46 per cent in ventilator-dependent patients under age 65, but not in patients 65 and older, the study indicated. When remestemcel-L was combined with the anti-inflammatory medication dexamethasone, it appeared to cut mortality by 75 per cent, compared to when dexamethasone was used alone.

An independent committee stopped the US trial in December after 222 patients had been enrolled, rather than the 300 planned, because the data monitoring board judged the study was unlikely to meet its primary endpoint of a 43 per cent reduction in death at 30 days.

Mesoblast shares plunged by more than a third on the news, and have declined further in the past few months, yesterday closing at a one-year low of $1.83.

At 10.18am this morning, Mesoblast shares were up 10.9 per cent to $2.03, still down significantly from over $5 in September.

On a conference call with analysts this morning, Mesoblast chief executive Dr Silviu Itescu called reduction in mortality exciting and very important and said that perhaps a different dosing regimen might be more effective in older patients, whom he noted have more comorbidities (health problems).

Itescu and chief medical officer Dr Fred Grossman said the company was still in discussions with the FDA about using remestemcel-L to treat graft-versus-host disease in children, a complication of bone marrow transplants.

But Itescu said it was too early to say whether Mesoblast would seek an emergency use authorisation with the FDA for using remestemcel-L as a COVID-19 treatment.

As noted, this study was stopped before its completion, and the signal detection work that weve done has been something thats very very important, and significant enough to warrant these discussions with the FDA for suitable paths forward, Dr Grossman said.

Theres no COVID-19 treatment that substantially reduces mortality, he said.

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Antiviral T cells protected, viable as off-the-shelf treatment for painful complication stem cells – Microbioz India

Infusion of T cells targeting BKV resulted in rapid responses, with 67.7% of patients seeing a complete or partial improvement in symptoms after 14 days. This increased to 81.6% of patients after 28 days post-infusion. No cases of grade 3 or grade 4 graft versus host disease (GVHD) or other infusion-related toxicities occurred.

Addressing a painful complication caused by BKV

BKV-associated hemorrhagic cystitis is an incredibly painful condition that causes significant morbidity in patients and can lead to worse cancer outcomes in the long term. Unfortunately, there are no effective treatments available. We were driven to develop this therapy to provide a better option for these patients, and this has emerged as a safe and effective therapy for patients at MD Anderson based on these results.

Katy Rezvani, M.D., Ph.D., Corresponding Author, Professor of Stem Cell Transplantation and Cellular Therapy

BKV is a human polyomavirus acquired by most people in early youth, Rezvani explained. Held in check by the immune system, BKV typically stays dormant in the cells lining the urinary tract, including the kidney, liver, bladder and ureters.

Allogeneic stem cell transplants, where stem cells come from a matched donor, require patients to be given therapies to suppress the immune system and protect against rejection. However, this can also trigger the BKV to start reproducing and cause severe cystitis, which could lead to hospitalization for days or months. An antiviral called cidofovir was used as a treatment but is associated with significant toxicities.

Recognizing that these viral infections can profoundly impact patient healing, Rezvani and her research team directed the development of antiviral T-cell therapies with the support of the MDS and AML Moon Shot, part of the institutions Moon Shots Program, a collaborative effort to quickly develop scientific discoveries into meaningful clinical improvements that save patients lives.

Starting with blood samples taken from healthy donors, the study team can isolate T cells and grow them to specifically recognize and target an assortment of antigens located on the BKV. These cells are expanded in the clinical good manufacturing practice (GMP) lab, under the direction of Elizabeth J. Shpall, M.D., professor of Stem Cell Transplantation and Cellular Therapy. From every donor, the team can fabricate anywhere from 20 to 50 doses of antiviral T cells, which can be stored until needed, Rezvani said.

In an earlier trial published in the New England Journal of Medicine, these researchers showed that BKV-specific T cells may effectively treat disease with the JC virus, a genetically similar polyomavirus which causes progressive multifocal leukoencephalopathy (PML), a rare and frequently fatal brain infection.

BKV-specific T cells get positive results in trialThe current trial enrolled a total of 59 MD Anderson patients experiencing BKV-HC after an allogeneic stem cell transplant. Women accounted for 40.7% of participants and men for 59.3%.

Patients received a single infusion of partially human leukocyte antigen (HLA)-matched T cells, with the option to get additional infusions every 2 weeks, if necessary.

Following infusion, the researchers did not observe any side effects which were probably attributed to the antiviral T cells. Several patients developed delayed cases of low-grade GVHD in the weeks and months after therapy, which were well within the expected rates of GVHD for these patients early after allogeneic stem cell transplant, Rezvani explained.

The median time for patients to have a partial response was 14 days, and the median time to complete response was 21 days. The estimated probability of achieving a complete response was almost 70% by day 45, indicating continuous activity of the infused cells. Responses were durable and no patients saw their symptoms return after a formerly achieved response.

After analyzing participants on the trial, the researchers determined that expansion of the infused T was positively correlated with individual responses.

Were extremely encouraged by the safety of the treatment and the fast answers we have seen in the vast majority of patients, Rezvani said. Because this method is so safe, we have been able to provide this therapy as an outpatient procedure as soon as patients start developing symptoms. This has been life-changing for the patients weve been able to treat thus far.

Ultimately, the researchers aim to validate these findings at a multi-institutional research and bring this treatment option to many more patients in need.

A complete list of cooperating authors and their disclosures are available with the full paper here. In addition to the Moon Shots Program, the study was supported by the National Institutes of Health (R01CA211044-05, CA016672).

Source:

Journal reference:

Olson, Z.,et al.(2021) Third-Party BK Virus-Specific Cytotoxic T Lymphocyte Therapy for Hemorrhagic Cystitis Following Allotransplantation.Journal of Clinical Oncology.doi.org/10.1200/JCO.20.02608.

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Antiviral T cells protected, viable as off-the-shelf treatment for painful complication stem cells - Microbioz India

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Desperate family of boy, 9, with leukaemia have 10 days to save his life… – The Sun

THE FAMILY of a nine-year-old leukaemia patient have been given 10 days to raise funds for life-saving treatment.

Nathaniel Nabenas family are appealing as he "clings on to life" after they were told they have until May 12 to find 201,000 for a stem cell transplant.

2

Without the operation, his cancer will be terminal.

Nathaniel is not entitled to free NHS treatment because he is not a British national.

He flew to the UK to have a 5,000 prosthetic eye fitted privately after losing it to a tumour in his home country Nigeria.

Doctors at Londons Great Ormond Street Hospital, moved by Nathaniels plight, have revealed they have waived their private consultant fees to help.

And Paul OGrady, who presents ITV series Little Heroes at the childrens hospital, has voiced his support.

It was only when he arrived here in November that doctors discovered he had acute myeloid leukaemia, a cancer so aggressive that he could have died within weeks without chemotherapy.

A stem cell match has been found but the family now have to find 201,103.

This money goes to the NHS for the cost of the transplant, treatment and after-care, based on a typical in-patient admission of eight weeks and a three-month follow-up as an outpatient.

2

Nathaniels cancer is in remission after six rounds of chemo but his consultant says it could return at any time.

If they raise enough, then a transplant will go ahead after tests due to take place on May 14.

Parents Ebisidor, a business analyst, and wife Modupe, 38, who are staying with family in Croydon, South London, were initially told the hospital bill could be as much as 825,000.

Ebisidor, 45, told the Mirror: Weve seen a dramatic turnaround from the hopeless situation we were in six months ago and we cant thank Sunday People readers enough.

Its incredible that the doctors are treating him in their private work without charging. They are wonderful. We are so grateful to everyone for giving us hope but at the same time asking people to help Nathaniel cling on to life. We know its a lot to ask.

Professor Ajay Vora, a consultant paediatric haematologist at GOSH, said the superhero fan had been incredibly brave.

But he warned: The cancer could come back at any time and the longer we wait the more likely it will return. Then Nathaniel will only have the option of palliative care.

"The tests we are doing in two weeks will reassure us it hasnt started to come back before we give him the transplant.

Prof Vora added: All the consultants involved in his care are working in a private capacity and have waived their fee because they want to help him.

Our time is not borrowed from the NHS because we are treating Nathaniel in our private service in our time.

Doctors had hoped Nathaniel would be able to have a bone marrow transplant from one of his two sisters Nadia, 11, and Nicole, 21 months. But they were not a match.

Instead, stem cells from a stored umbilical cord will be used to save him.

Doctors will give Nathaniel high doses of chemotherapy to kill off his stem cells and replace them with healthy ones.

Dad Ebisidor said: The faster we can do this transplant the more chance Nathaniel has of survival.

"We dont have this sort of treatment back home. We didnt bring him to the UK sick. He got poorly while he was here. If the operation doesnt work our only option will be to take him to a hospice.

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By law, non-UK residents get free emergency care but are charged for operations if they are admitted to hospital.

They pay for treatment at 150% of the NHS national tariff the cost normally incurred for eligible patients.

A Great Ormond Street spokesman said: Nathaniel has responded well to treatment, with our clinical teams working to provide the best care for him including looking at taking advantage of the short window of time for receiving a transplant.

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Desperate family of boy, 9, with leukaemia have 10 days to save his life... - The Sun

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Orchard Therapeutics Announces Multiple Presentations at the 24th Annual Meeting of the American Society of Gene & Cell Therapy – GlobeNewswire

Seven abstracts accepted show the potential of HSC gene therapy to transform the treatment of multiple severe rare disorders

First peer-reviewed presentation from companys work in transduction enhancers showcases promise to improve manufacturing efficiency of lentiviral-based gene therapy

BOSTON and LONDON, April 28, 2021 (GLOBE NEWSWIRE) -- Orchard Therapeutics(Nasdaq: ORTX), a global gene therapy leader, today announced the acceptance of seven abstracts at the 24th Annual Meeting of the American Society of Gene & Cell Therapy (ASGCT) taking place virtually from May 11-14. Accepted abstracts include clinical data from several of its hematopoietic stem cell (HSC) gene therapy programs, including: OTL-203, being investigated for the treatment of mucopolysaccharidosis type I (MPS-I), and OTL-101, being investigated for the treatment of adenosine deaminase severe combined immunodeficiency (ADA-SCID), as well as the companys efforts to improve efficiency of HSC gene therapy manufacturing though the development of proprietary transduction enhancers.

Our significant presence at ASGCT this year showcases not only the depth and breadth of our HSC gene therapy pipeline and the strength of our clinical data but also how we are using innovation to improve the way our HSC gene therapies will be manufactured in the future, said Bobby Gaspar, M.D., Ph.D., chief executive officer of Orchard Therapeutics. These data demonstrate the transformative potential of HSC gene therapy and, along with our partners, we look forward to sharing results with the broader scientific and medical communities.

The presentations are listed below, and the full preliminary program is available online on the ASGCT website.

Oral Presentation Details:

Development of an optimized lentiviral transduction process for ex vivo CD34+ hematopoietic stem cell gene therapy drug product manufactureAbstract Number: 1Presenting Author: Pervinder Sagoo, Ph.D., Orchard TherapeuticsDate/Time: Tuesday, May 11 at 5:30 p.m. EDT

Autologous ex vivo lentiviral gene therapy for the treatment of ADA-SCIDAbstract Number: 40Presenting Author: Claire Booth, Ph.D., UCL GOSH Institute of Child HealthDate/Time: Tuesday, May 11 at 6:30 p.m. EDT

Immune reconstitution in transfusion dependent beta-thalassemia patients treated with hematopoietic stem cell gene therapyAbstract Number: 79Presenting Author: Samantha Scaramuzza, Ph.D., San Raffaele Telethon Institute for Gene TherapyDate/Time: Wednesday, May 12 at 5:45 p.m. EDT

Hematopoietic reconstitution and lineage commitment in HSC gene therapy patients are influenced by the disease backgroundAbstract Number: 82Presenting Author: Andrea Calabria, Ph.D., San Raffaele Telethon Institute for Gene TherapyDate/Time: Wednesday, May 12 at 6:30 p.m. EDT

Liquid-biopsy-integration-site-sequencing allows safety studies and longitudinal monitoring of vector integration sites in LV and AAV-based in-vivo GT applicationsAbstract Number: 250Presenting Author: Daniela Cesana, Ph.D., San Raffaele Telethon Institute for Gene TherapyDate/Time: Friday, May 14 at 12:15 p.m. EDT

Ex vivo hematopoietic stem cell gene therapy for mucopolysaccharidosis type I (Hurler syndrome): An interim analysis with a median follow up of 19 monthsAbstract Number: 219Presenting Author: Bernhard Gentner, M.D., San Raffaele Telethon Institute for Gene TherapyDate/Time: Friday, May 14 at 1:15 p.m. EDT

Poster Presentation Details:

Dissecting bone remodeling mechanisms and hematopoietic stem cell gene therapy impact in mucopolysaccharidosis type I Hurler bone defects Abstract Number: 609Presenting Author: Ludovica Santi, Ph.D., San Raffaele Telethon Institute for Gene TherapyDate/Time: Tuesday, May 11 at 8:00 a.m. EDT

About Orchard TherapeuticsOrchard Therapeutics is a global gene therapy leader dedicated to transforming the lives of people affected by rare diseases through the development of innovative, potentially curative gene therapies. Our ex vivo autologous gene therapy approach harnesses the power of genetically modified blood stem cells and seeks to correct the underlying cause of disease in a single administration. In 2018, Orchard acquired GSKs rare disease gene therapy portfolio, which originated from a pioneering collaboration between GSK and theSan Raffaele Telethon Institute for Gene Therapy in Milan, Italy. Orchard now has one of the deepest and most advanced gene therapy product candidate pipelines in the industry spanning multiple therapeutic areas where the disease burden on children, families and caregivers is immense and current treatment options are limited or do not exist.

Orchard has its global headquarters in London and U.S. headquarters in Boston. For more information, please visit http://www.orchard-tx.com, and follow us on Twitter and LinkedIn.

Availability of Other Information About OrchardInvestors and others should note that Orchard communicates with its investors and the public using the company website (www.orchard-tx.com), the investor relations website (ir.orchard-tx.com), and on social media (Twitter andLinkedIn), including but not limited to investor presentations and investor fact sheets,U.S. Securities and Exchange Commissionfilings, press releases, public conference calls and webcasts. The information that Orchard posts on these channels and websites could be deemed to be material information. As a result, Orchard encourages investors, the media, and others interested in Orchard to review the information that is posted on these channels, including the investor relations website, on a regular basis. This list of channels may be updated from time to time on Orchards investor relations website and may include additional social media channels. The contents of Orchards website or these channels, or any other website that may be accessed from its website or these channels, shall not be deemed incorporated by reference in any filing under the Securities Act of 1933.

Forward-looking StatementsThis press release contains certain forward-looking statements about Orchards strategy, future plans and prospects, which are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements include express or implied statements relating to, among other things, Orchards business strategy and goals, and the therapeutic potential of Orchards product candidates, including the product candidate or candidates referred to in this release. These statements are neither promises nor guarantees and are subject to a variety of risks and uncertainties, many of which are beyond Orchards control, which could cause actual results to differ materially from those contemplated in these forward-looking statements. In particular, these risks and uncertainties include, without limitation: the risk that prior results, such as signals of safety, activity or durability of effect, observed from preclinical studies or clinical trials will not be replicated or will not continue in ongoing or future studies or trials involving Orchards product candidates, will be insufficient to support regulatory submissions or marketing approval in the US or EU, as applicable, or that long-term adverse safety findings may be discovered; the risk that any one or more of Orchards product candidates, including the product candidates referred to in this release, will not be approved, successfully developed or commercialized; the risk of cessation or delay of any of Orchards ongoing or planned clinical trials; the risk that Orchard may not successfully recruit or enroll a sufficient number of patients for its clinical trials; the delay of any of Orchards regulatory submissions; the failure to obtain marketing approval from the applicable regulatory authorities for any of Orchards product candidates or the receipt of restricted marketing approvals; the inability or risk of delays in Orchards ability to commercialize its product candidates, if approved, or Libmeldy in the EU; the risk that the market opportunity for Libmeldy, or any of Orchards product candidates, may be lower than estimated; and the severity of the impact of the COVID-19 pandemic on Orchards business, including on clinical development, its supply chain and commercial programs. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements.

Other risks and uncertainties faced by Orchard include those identified under the heading "Risk Factors" in Orchards Annual Report on Form 10-K for the year endedDecember 31, 2020, as filed with theU.S. Securities and Exchange Commission(SEC), as well as subsequent filings and reports filed with theSEC. The forward-looking statements contained in this press release reflect Orchards views as of the date hereof, and Orchard does not assume and specifically disclaims any obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events or otherwise, except as may be required by law.

Contacts

InvestorsRenee LeckDirector, Investor Relations+1 862-242-0764Renee.Leck@orchard-tx.com

MediaBenjamin NavonDirector, Corporate Communications+1 857-248-9454Benjamin.Navon@orchard-tx.com

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Orchard Therapeutics Announces Multiple Presentations at the 24th Annual Meeting of the American Society of Gene & Cell Therapy - GlobeNewswire

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Investigating CAR T-Cell Therapy for Use in Different Disease Types – Targeted Oncology

Michael Bishop, MD, a professor of medicine and director of Hematopoietic Stem Cell Transplantation Program at The University of Chicago Medicine, discusses the investigations of and responses to chimeric antigen receptor (CAR) T-cell therapy in different disease types.

One of the settings furthest along in exploring the use of CAR T cells is non-Hodgkin lymphoma, with about 40% to 50% patients are achieving sustainable complete responses with CAR T-cell therapy. There are still significant areas that can be improved upon for this patient population, according to Bishop.

Another disease type where there is potential opportunity to use CAR T cells is acute lymphoblastic leukemia. Bishop says there has been success for children in this setting, and now there is study for adults that will be reporting out soon called the ZUMA-3 trial (NCT02614066), which investigated brexucabtagene autoleucel (KTE-X19). Other studies are looking at the use of allogeneic CAR T-cell therapy in patients with acute lymphoblastic leukemia.

There are also trials in multiple myeloma looking at CAR T-cell therapy. Bishop feels the results for this patient population appear to be very exciting, with higher and more sustained complete response rates, and there is an opportunity to further improve upon those results.

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Investigating CAR T-Cell Therapy for Use in Different Disease Types - Targeted Oncology

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Enhanced inhibition of tumor growth using TRAIL-overexpressing adipose-derived stem cells in combination with the chemotherapeutic agent CPT-11 in…

This article was originally published here

Prostate Int. 2021 Mar;9(1):31-41. doi: 10.1016/j.prnil.2020.07.002. Epub 2020 Jul 31.

ABSTRACT

BACKGROUND: This study investigated the inhibition of tumor growth in castrate-resistant prostate cancer (CRPC)-bearing mice by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-overexpressing adipose-derived stem cells (ADSCs) (hTERT-ADSC.sTRAIL), which was enhanced by combined treatment with CPT-11.

MATERIALS AND METHODS: An hTERT-ADSC.sTRAIL cell line was established by transfection with a lentiviral vector (CLV-Ubic) encoding the human sTRAIL gene. Quantitative polymerase chain reaction and Western blots were performed to confirm gene overexpression. An invasion study for the selective migration ability toward PC3 cells was performed. In the in vivo study, the tumor volume in mice treated with ADSC. sTRAIL and CPT-11 was measured.

RESULTS: Carboxylesterase was generated from hTERT-ADSCs. The gene expression of sTRAIL from hTERT-ADSC.sTRAIL was shown. The directional migration of ADSC.sTRAIL cells toward PC3 cells was significantly stimulated by PC3 cells in vitro (P < 0.05). In the in vitro study, the viability of PC3 cells significantly decreased in the presence of ADSC.sTRAIL (62.7 2.0%) and CPT-11 compared with that of CPT-11 alone (83.0 1.0%) at a cell ratio as low as 0.05 (PC3: ADSC.sTRAIL) (P < 0.05). The proportion of apoptotic PC3 cells significantly increased in the presence of ADSC.sTRAIL (37.2 2.1%) and CPT-11 compared with that of CPT-11 alone (16.5 1.0%) (P < 0.05). In the in vivo study, the inhibition of tumor growth in CRPC-bearing mice by TRAIL-overexpressing adipose stem cells was enhanced by combined treatment with the chemotherapeutic agent CPT-11 compared with that in the treatment with cpt-11 alone. Immunohistochemical staining of the removed tumors showed anti-TRAIL-positive cells and apoptotic bodies after hTERT-ADSC.sTRAIL treatment or combined treatment with hTERT-ADSC.sTRAIL and CPT-11.

CONCLUSIONS: Therapeutic stem cells expressing sTRAIL genes combined with CPT-11 can provide a new strategy for treating CRPC in clinical trials using the patients own ADSCs.

PMID:33912512 | PMC:PMC8053698 | DOI:10.1016/j.prnil.2020.07.002

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Enhanced inhibition of tumor growth using TRAIL-overexpressing adipose-derived stem cells in combination with the chemotherapeutic agent CPT-11 in...

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Thomas Smeenk on Hemostemix’s autologous stem cell therapy technology and why some call it ‘the fountain of youth’ – InvestorIntel

In a recent InvestorIntel interview, Tracy Weslosky spoke with Thomas Smeenk, Co-Founder, President and CEO of Hemostemix Inc. (TSXV: HEM | OTC: HMTXF), about Hemostemixs autologous stem cell therapy and why he calls the technology the fountain of youth.

In this InvestorIntel interview, which may also be viewed on YouTube (click here to subscribe to the InvestorIntel Channel), Thomas went on to say that Hemostemixs lead product ACP-01 works by treating ischemia (lack of blood circulation) in a patients body. The technology has already been used to treat around 500 patients suffering from ischemia in the heart, arteries, and limb. He added that using the technology many patients were able to save their limbs from otherwise certain amputations. Hemostemix has 91 patents including a patent on the automation of production which enables the company to scale the business exponentially as over a million patients lose their limbs to amputation in North America alone. The technology is now in Phase 2 clinical trial.

To watch the full interview,click here

About Hemostemix Inc.

Hemostemix is a publicly traded autologous stem cell therapy company. A winner of the World Economic Forum Technology Pioneer Award, the Company developed and is commercializing its lead product ACP-01 for the treatment of CLI, PAD, Angina, Ischemic Cardiomyopathy, Dilated Cardiomyopathy and other conditions of ischemia. ACP-01 has been used to treat over 300 patients, and it is the subject of a randomized, placebo-controlled, double blind trial of its safety and efficacy in patients with advanced critical limb ischemia who have exhausted all other options to save their limb from amputation.

On October 21, 2019, the Company announced the results from its Phase II CLI trial abstract entitled Autologous Stem Cell Treatment for CLI Patients with No Revascularization Options: An Update of the Hemostemix ACP-01 Trial With 4.5 Year Followup which noted healing of ulcers and resolution of ischemic rest pain occurred in 83% of patients, with outcomes maintained for up to 4.5 years.

The Company owns 91 patents across five patent families titled: Regulating Stem Cells, In Vitro Techniques for use with Stem Cells, Production from Blood of Cells of Neural Lineage, and Automated Cell Therapy.

To know more about Hemostemix Inc.,click here

Disclaimer:Hemostemix Inc. is an advertorial member of InvestorIntel Corp.

Thisinterview, which was produced by InvestorIntel Corp. (IIC)does not contain, nor does it purport to contain, a summary of all the material information concerning theCompany being interviewed. IIC offers no representations or warranties that any of the information contained in this interview is accurate or complete.

This presentationmay containforward-looking statements within the meaning ofapplicable Canadian securities legislation.Forward-looking statements are based on the opinions and assumptions of managementof the Companyas of the date made. Theyare inherently susceptible to uncertainty and other factors that could cause actual events/results to differ materially from these forward-looking statements.Additional risks and uncertainties, including those that the Company does not know about now or that it currently deems immaterial, may also adversely affect the Companys business or any investment therein.

Anyprojectionsgivenare principally intended for use as objectives and are not intended, and should not be taken, as assurances that the projected results will be obtained by the Company.The assumptions used may not prove to be accurateanda potential decline in the Companys financial condition or results of operations may negatively impact the value of its securities. Prospectiveinvestors are urged to review the Companys profile onwww.Sedar.comand to carry out independent investigations in order to determine their interest in investing in the Company.

If you have any questions surrounding the content of this interview, please emailinfo@investorintel.com.

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Thomas Smeenk on Hemostemix's autologous stem cell therapy technology and why some call it 'the fountain of youth' - InvestorIntel

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Monitoring levels of vimentin-positive circulating cancer stem cells and tumor cells in patients with advanced EGFR-mutated non-small cell lung cancer…

This article was originally published here

Lung Cancer. 2021 Apr 18;156:50-58. doi: 10.1016/j.lungcan.2021.04.014. Online ahead of print.

ABSTRACT

OBJECTIVES: Circulating tumor cells (CTCs) are associated with tumor spread, whereas cancer stem cells may be related to drug resistance. However, few studies have analyzed the levels of circulating cancer stem cells (CCSCs) and CTCs in patients with advanced non-small cell lung cancer (NSCLC).

MATERIALS AND METHODS: Treatment-nave patients with EGFR-mutated NSCLC who received epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy were recruited prospectively. The cell surface vimentin antibody was used for CTC detection and CD133 antibody for CCSC detection. CCSC and CTC levels were measured as cell count per 4 mL of blood, before treatment, after 2 and 12 weeks of treatment, and at disease progression. Data on clinical characteristics and outcomes were also collected.

RESULTS: At diagnosis (n = 29), the median CCSC and CTC levels were 0 (interquartile range, 0-2) and 3 (2-9), respectively. After 12 weeks, the CCSC and CTC levels were lower than those at diagnosis (CCSC: 0 (0-0), p = 0.14; CTC: 1 (0-4), p = 0.048). At disease progression, the median CCSC and CTC levels were 0 (0-1) and 1 (0-2), respectively. Patients with higher CCSC and CTC levels at diagnosis had a numerically shorter progression-free survival.

CONCLUSION: In patients with EGFR-mutated NSCLC, CCSC and CTC levels became lower after 12 weeks of EGFR-TKI therapy and remained low at disease progression. High pre-treatment CCSC and CTC levels may be associated with a trend towards poor treatment outcomes.

PMID:33894494 | DOI:10.1016/j.lungcan.2021.04.014

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Monitoring levels of vimentin-positive circulating cancer stem cells and tumor cells in patients with advanced EGFR-mutated non-small cell lung cancer...

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Fate Therapeutics Announces Four Presentations at the 2021 ASGCT Annual Meeting – GlobeNewswire

Two Oral Presentations to Cover iPSC-derived Cell-based Cancer Immunotherapy Pipeline

Company to Host Investor Event on May 13 to Highlight Interim Phase 1 Clinical Data from the Companys FT516 and FT538 Programs for Relapsed / Refractory AML

SAN DIEGO, April 27, 2021 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, today announced that two oral and two digital presentations of the Companys induced pluripotent stem cell (iPSC) product platform were accepted for presentation at the 24th American Society of Gene & Cell Therapy Annual Meeting (ASGCT) being held virtually from May 11-14, 2021.

In addition to the Companys presentations at ASGCT, its iPSC-derived natural killer (NK) cell product pipeline is expected to be featured in a meeting symposium on May 11 by Jeffrey S. Miller, M.D., Professor of Medicine, University of Minnesota and Deputy Director of the Masonic Cancer Center and scientific advisor and collaborator of the Company, and its iPSC-derived CAR T-cell product platform is expected to be highlighted during the meetings plenary session on May 12 by Michel Sadelain, M.D., Ph.D., Stephen and Barbara Friedman Chair and Director, Center for Cell Engineering, Memorial Sloan Kettering Cancer Center and collaborator of the Company.

The Company also plans to host a virtual investor event on May 13 to highlight interim Phase 1 clinical data from its FT516 and FT538 programs for the treatment of relapsed / refractory acute myeloid leukemia (AML). The Phase 1 clinical trial of FT516 has enrolled the first and second dose cohorts (90 million and 300 million cells per dose, respectively), and dose escalation is ongoing in the third dose cohort (900 million cells per dose). The Phase 1 clinical trial of FT538 is ongoing in the first dose cohort (100 million cells per dose).

ASGCT Oral Presentations

ASGCT Digital Presentations

About Fate Therapeutics iPSC Product PlatformThe Companys proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Companys first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Companys platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT516FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG1 antibodies. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in a multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-targeted monoclonal antibodies for the treatment of advanced B-cell lymphoma (NCT04023071). Additionally, FT516 is being investigated in a multi-dose Phase 1 clinical trial in combination with avelumab for the treatment of advanced solid tumor resistant to anti-PDL1 checkpoint inhibitor therapy (NCT04551885).

About FT538FT538 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three functional components: a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence and function in high oxidative stress environments. FT538 is designed to enhance innate immunity in cancer patients, where endogenous NK cells are typically diminished in both number and function due to prior treatment regimens and tumor suppressive mechanisms. In preclinical studies, FT538 has shown superior NK cell effector function, as compared to peripheral blood NK cells, with the potential to confer significant anti-tumor activity to patients through multiple mechanisms of action. FT538 is being investigated in a multi-dose Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and in combination with daratumumab, a CD38-targeted monoclonal antibody therapy, for the treatment of multiple myeloma (NCT04614636).

About Fate Therapeutics, Inc.Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for patients with cancer. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Companys immuno-oncology pipeline includes off-the-shelf, iPSC-derived natural killer (NK) cell and T-cell product candidates, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens using chimeric antigen receptors (CARs). The Companys pipeline also includes ProTmune, a pharmacologically modulated, donor cell graft that is currently being evaluated in a Phase 2 clinical trial for the prevention of graft-versus-host disease in patients with hematologic malignancies undergoing allogeneic stem cell transplant. Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.fatetherapeutics.com.

Forward-Looking StatementsThis release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the Companys clinical studies and preclinical research and development programs. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that results observed in prior studies of its product candidates, including preclinical studies and clinical trials of any of its product candidates, will not be observed in ongoing or future studies involving these product candidates, and the risk that the Company may cease or delay preclinical or clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials or to support regulatory approval, difficulties or delays in subject enrollment in current and planned clinical trials, difficulties in manufacturing or supplying the Companys product candidates for clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development). For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Companys actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Companys periodic filings with the Securities and Exchange Commission, including but not limited to the Companys most recently filed periodic report, and from time to time in the Companys press releases and other investor communications.Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.

Contact:Christina TartagliaStern Investor Relations, Inc.212.362.1200christina@sternir.com

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Fate Therapeutics Announces Four Presentations at the 2021 ASGCT Annual Meeting - GlobeNewswire

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