CytoMed Therapeutics Limited has successfully completed the first dose level of its groundbreaking Phase I clinical trial for CTM-N2D, a novel allogeneic CAR gamma delta T cell therapy, marking a significant milestone in cancer immunotherapy development. The Singapore-based biopharmaceutical company announced that four late-stage cancer patients have completed dose level 1 of the ANGELICA trial (NCT05302037), with dose level 2 scheduled to begin in the third quarter of 2025.
Revolutionary Approach to CAR-T Therapy
The ANGELICA trial represents a first-in-human Phase I dose-escalation study evaluating the safety and tolerability of allogeneic NKG2DL-targeting chimeric antigen receptor-grafted (CAR) gamma delta T cells. This innovative approach addresses a basket of cancer indications including advanced solid and hematological malignancies.
CTM-N2D utilizes gamma delta T cells derived from healthy donors, which are expanded and modified to express CARs that target NKG2DL antigens commonly present in many cancers. A key advantage of this therapy is that CTM-N2D can be infused into patients without the need for donor-patient compatibility matching, potentially streamlining treatment delivery and reducing costs.
Differentiation from Conventional CAR-T Therapies
This approach differs significantly from conventional CAR-αβ T cell therapies, which typically involve collecting a patient's own blood cells and modifying them to express cancer-targeting CARs before re-infusion. The modified αβ T cells are then re-infused back into the patient to target and kill cancer cells.
Unlike chemotherapy that targets all actively dividing cells including healthy ones, CAR-T cells specifically recognize targets (antigens) present on cancer cells to kill them. CytoMed's gamma delta T cell approach potentially offers advantages in terms of manufacturing efficiency and treatment accessibility.
Company Background and Technology Platform
Incorporated in 2018, CytoMed was spun off from the Agency for Science, Technology and Research (A*STAR), Singapore's leading research and development agency in the public sector. The company focuses on harnessing its licensed proprietary technologies, including gamma delta T cell and iPSC-derived gamma delta Natural Killer T cell platforms, to create novel cell-based allogeneic immunotherapies for various human cancers.
The development of these novel technologies has been inspired by the clinical success of existing CAR-T therapies in treating hematological malignancies, as well as addressing current clinical limitations and commercial challenges in extrapolating the CAR-T principle into the treatment of solid tumors.
Clinical Trial Progress and Future Plans
The successful completion of dose level 1 in four patients represents a crucial safety milestone for the ANGELICA trial. The study's basket design allows for evaluation across multiple cancer types, potentially broadening the therapeutic impact of CTM-N2D if proven safe and effective.
As the trial progresses to dose level 2, CytoMed will continue to evaluate the safety and tolerability profile of CTM-N2D while gathering preliminary efficacy data. The company's allogeneic approach could potentially offer advantages in terms of treatment accessibility and cost-effectiveness compared to autologous CAR-T therapies currently on the market.
