Latest news with #TILs
Medscape
01-07-2025
- Health
- Medscape
CISH-Targeted TILs Show Promise in GI Cancer Trial
This transcript has been edited for clarity. Hello. I'm David Kerr, professor of cancer medicine at University of Oxford. I'd like to talk a little about a phase 1 trial that has just been published in the May edition of Lancet Oncology , a beautiful paper by Emil Lou and colleagues, in which they all looked at an extraordinarily complicated regimen of gene editing and then reinfusing tumor-infiltrating lymphocytes (TILs). This just shows how remarkable modern cancer medicine can be. I'd like to talk a little about the procedures involved, given the route of complexity. Initially, for patients in the phase 1 trial with metastatic advanced gastrointestinal cancer, the first step was to receive a non-myeloablative lymphocyte-depletion chemotherapy. This is cyclophosphamide and fludarabine. This is then followed by high-dose interleukin-2. The process of producing the gene-edited TILs is absolutely fascinating. The gene-editing target, the gene that we wanted to knock down, was a novel, internal immune checkpoint protein gene, CISH , which encoded a cytokine-inducible SH2 domain-containing protein. This is an internal immune checkpoint target and quite an interestingly novel one. That's the target to knock down. The process of building the therapy is completely fascinating. Autologous TILs were generated from tumor biopsy fragments from each individual patient, and samples of the TILs were then cultured with patient-derived lymphoblastic cell lines, ormonocyte-derived dendritic cells loaded with pools of synthetic 25-mer peptides containing tumor-specific mutations that were detected from whole-exome sequencing from the patient's tumor. Think about that for a second. The patients undergo biopsy. The TILs are taken off for culture — more on that later — but they were co-cultured with a source of patient-specific tumor-associated antigens, which were generated by whole-exome sequencing. Then, using 25-mer fragments of what they felt were the key tumor-specific antigens, were plumbed into the patients' own dendritic cells so that these antigens would be presented to at the time of co-culture with a patient, so in TILs. It boggles the mind. The TILs with demonstrated reactivity to the neoantigens in this co-culture experiment were selected and they were then subjected to the CRISPR gene editing in vitro. They knocked down CISH , the target that they were aiming for. Then the edited TILs underwent a rapid expansion protocol. They were cryopreserved, and then via some very sophisticated molecular quality control, infused back into the patients. Goodness gracious — I mean, it's extraordinary when you think about it. It was a phase 1 trial, so dose-escalating the number of cells. It's pretty well tolerated. As you would expect, there was some fatigue and some fever. Nobody died in the back of any of the treatment that was given in that way. In terms of effectiveness, these were patients with advanced disease who had undergone multiple previous lines of treatment. There were no severe cytokine-release syndromes, nothing of grade 3 or worse. No neurotoxicity. Six of 12 patients had stable disease by day 28. Four (33%) had stable disease ongoing at 56 days. One young adult who had microsatellite-unstable and mismatch repair-deficient MSI-high tumors — therefore they've already got an existing high neoantigen load — had a complete response. That was very pleasing. I say, again, this is an extraordinary piece of work, to think about the complexity involved in every step of that process — before the patients' own cells, the autologous cells, were manipulated and reinfused with moderately acceptable toxicity, I would say. It's a phase 1 trial, so you're not really looking for a big efficacy readout, but the one younger patient who had, if you like, a genetic predisposition to responding to immunotherapy anyway, had a complete response. I'd be really interested in what you think about it. Who knows what the cost of that would be in terms of the complexity — I keep using that word, don't I? — of every single step. Modern cancer medicine — don't you love it? Well done to the team for producing this phase 1 trial result. How generalizable it will be remains to be seen, given the multiple different steps that are required. It just shows you how, in my lifetime as a cancer doctor, four decades, remarkable progress has been. I'm very interested in any comments you'd have to make. As always, thanks for listening. For the time being, Medscapers, ahoy, and over and out.
Globe and Mail
23-05-2025
- Business
- Globe and Mail
Oncolytics Biotech® to Present New Clinical Trial Data at ASCO Showing Pelareorep's Unique Immune Activation Capabilities
Pelareorep initiates a pro-inflammatory tumor microenvironment (TME) and induces innate and adaptive immune responses New analyses confirm that pelareorep primes the TME to allow circulating tumor-infiltrating lymphocytes (TILs) in the blood to attack tumors Pre-existing TIL clones in plasma may correlate positively with tumor shrinkage in pancreatic cancer SAN DIEGO and CALGARY, AB , May 23, 2025 /CNW/ -- Oncolytics Biotech ® Inc. (NASDAQ: ONCY) (TSX: ONC), a leading clinical-stage company specializing in immunotherapy for oncology, today announced new data from the Phase I/II GOBLET clinical trial in a poster presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. The presentation highlights pelareorep's mechanism of action in pancreatic ductal adenocarcinoma (PDAC), offering new insights into how this immunotherapy stimulates multiple arms of the immune system and primes tumors for treatment. "For the first time, we're able to map the cascade of immune responses stimulated by pelareorep," said Thomas Heineman , M.D., Ph.D., Chief Medical Officer for Oncolytics Biotech. "It starts with the expansion of anti-reovirus T cells, followed by the upregulation of chemokines that mediate the expansion of pre-existing TIL clones in the blood. These T cells can now return to the tumor and attack it, resulting in a reduction in tumor size. Pelareorep-mediated upregulation of chemokines also makes the tumor microenvironment immunologically active and able to actively recruit cancer-specific T cells to the tumor. These findings deepen our understanding of pelareorep's ability to convert immunologically cold tumors into immunologically active ones that may benefit from pelareorep-based combination therapy." Abstract Number: 2562 Title: Role of pelareorep in activating anti-tumor immunity in PDAC. Presentation Type: Poster Session Title: Developmental Therapeutics – Immunotherapy Session Date and Time: June 2, 2025 , 1:30 - 4:30 p.m. CT A copy of the ASCO presentation will be available on the Media page of Oncolytics' website ( LINK) following the conclusion of the meeting. Highlights from the poster and abstract include: Pelareorep initiates the expansion of reovirus-specific T cells that are associated with favorable clinical responses at week 24 Pelareorep increases cytokines and chemokines associated with altering the TME to allow anti-viral and anti-tumor T cells to attack the tumor The presence of TIL clones in the blood before treatment and the expansion of these clones in the blood post-treatment are associated with favorable clinical responses Previously reported efficacy results from GOBLET Cohort 1, which is evaluating the therapeutic regimen of pelareorep, nab-paclitaxel, gemcitabine, and atezolizumab (Tecentriq ®) in first-line metastatic PDAC patients, showed a 62% overall response rate, an 85% disease control rate, and a 45% 12-month survival rate About GOBLET The GOBLET ( G astrointestinal tum O rs exploring the treatment com B inations with the oncolytic reovirus pe L ar E orep and an T i-PD-L1) study is a phase 1/2 multiple indication study in advanced or metastatic gastrointestinal tumors. The study is being conducted at 17 centers in Germany and is being managed by AIO-Studien-gGmbH. The primary endpoints of the study are objective response rate (ORR) and/or disease control rate assessed at week 16 and safety. Key secondary and exploratory endpoints include additional efficacy assessments and evaluation of potential biomarkers. The study comprises five treatment groups: Pelareorep in combination with atezolizumab, gemcitabine, and nab-paclitaxel in 1 st line advanced/metastatic pancreatic cancer patients; Pelareorep in combination with atezolizumab in 1 st line MSI (microsatellite instability)-high metastatic colorectal cancer patients; Pelareorep in combination with atezolizumab and TAS-102 in 3 rd line metastatic colorectal cancer patients Pelareorep in combination with atezolizumab in 2 nd line advanced and unresectable anal cancer patients; and Pelareorep in combination with modified FOLFIRINOX with and without atezolizumab in newly diagnosed metastatic PDAC patients. Any cohort meeting pre-specified efficacy criteria in Stage 1 may be advanced to Stage 2 and enroll additional patients. About AIO AIO-Studien-gGmbH (AIO) emerged from the study center of the medical oncology working group within the German Cancer Society (DKG). AIO operates with a non-profit purpose of promoting science and research with a focus on medical oncology. Since its foundation, AIO has become a successful sponsor and study management company and has established itself both nationally and internationally. About Oncolytics Biotech Inc. Oncolytics is a clinical-stage biotechnology company developing pelareorep, an intravenously delivered immunotherapeutic agent. Pelareorep has demonstrated promising results in two randomized Phase 2 studies in metastatic breast cancer and Phase 1 and 2 studies in pancreatic cancer. It acts by inducing anti-cancer immune responses and promotes an inflamed tumor phenotype -- turning "cold" tumors "hot" -- through innate and adaptive immune responses to treat a variety of cancers. Pelareorep has demonstrated synergies with multiple approved oncology treatments. Oncolytics is currently conducting and planning combination clinical trials with pelareorep in solid malignancies as it advances towards registrational studies in metastatic breast cancer and pancreatic cancer, both of which have received Fast Track designation from the FDA. For more about Oncolytics, please visit: or follow the company on social media on LinkedIn and on X @ oncolytics. Tecentriq ® (atezolizumab) is a registered trademark of Genentech, a member of the Roche Group. This press release contains forward-looking statements, within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended and forward-looking information under applicable Canadian securities laws (such forward-looking statements and forward-looking information are collectively referred to herein as "forward-looking statements"). Forward-looking statements contained in this press release include statements regarding Oncolytics' belief as to the potential, mechanism of action and benefits of pelareorep as a cancer therapeutic; and other statements related to anticipated developments in Oncolytics' business and technologies. In any forward-looking statement in which Oncolytics expresses an expectation or belief as to future results, such expectations or beliefs are expressed in good faith and are believed to have a reasonable basis, but there can be no assurance that the statement or expectation or belief will be achieved. Such forward-looking statements involve known and unknown risks and uncertainties, which could cause Oncolytics' actual results to differ materially from those in the forward-looking statements. Such risks and uncertainties include, among others, the availability of funds and resources to pursue research and development projects, the efficacy of pelareorep as a cancer treatment, the success and timely completion of clinical studies and trials, Oncolytics' ability to successfully commercialize pelareorep, uncertainties related to the research and development of pharmaceuticals, uncertainties related to the regulatory process and general changes to the economic environment. We may incur expenses or delays relating to events outside of our control, which could have a material adverse impact on our business, operating results and financial condition. Investors should consult Oncolytics' quarterly and annual filings with the Canadian and U.S. securities commissions for additional information on risks and uncertainties relating to the forward-looking statements. Investors are cautioned against placing undue reliance on forward-looking statements. The Company does not undertake any obligation to update these forward-looking statements, except as required by applicable laws. Company Contact Jon Patton Director of IR & Communication jpatton@ Investor Relations for Oncolytics Mike Moyer LifeSci Advisors +1-617-308-4306 mmoyer@ Media Contact for Oncolytics Michael Rubenstein LifeSci Communications mrubenstein@
