In a positive development for cancer treatment innovation, CytoMed Therapeutics (NASDAQ: GDTC) has initiated the ANGELICA Trial with its first patient dosing in Singapore, marking an important milestone in cell therapy research. This phase I clinical trial represents a novel development in donor blood-derived allogeneic off-the-shelf cancer cell therapy for both liquid and solid cancers, particularly in addressing accessibility challenges in advanced treatments.
Breaking New Ground in CAR-T Cell Therapy
Traditional CAR-T cell treatments require harvesting and modifying a patient's own T cells—a process that involves considerable time and resources. CytoMed's platform takes a different approach by utilizing the rare gamma delta T cells (γδ T cells) from healthy donors. These specialized immune cells, which comprise only 1–5% of a person's T cell population, possess natural anti-cancer properties and can be used as an affordable cellular platform to create standardized universal treatments in combination with drugs to boost efficacy.
The ANGELICA Trial (NCT05302037), which received clinical trial authorization from Singapore's Health Sciences Authority, evaluates allogeneic NKG2DL-targeting chimeric antigen receptor-grafted (CAR) gamma delta T cells (CTM-N2D) in patients with advanced solid tumors or hematological malignancies. This trial represents a significant step forward in evaluating the potential of allogeneic cell therapy for multiple cancer types.
The Science Behind the Innovation
At the core of CytoMed's technology is its unique platform approach to cell therapy. While traditional CAR-T cell therapies focus on αβ T cells, which require onerous matching between donor and recipient, γδ T cells possess inherent properties that make them suitable for allogeneic (donor-to-patient) treatments:
Natural Cancer Recognition: γδ T cells can naturally identify and target stressed or malignant cells without requiring extensive genetic modification.
Reduced Risk Profile: These cells demonstrate a significantly lower risk of triggering graft-versus-host disease, a common complication in cell therapies, especially cytokine release syndrome.
Broader Application: The cells' ability to recognize multiple stress signals makes them effective against various cancer types, potentially offering a more versatile treatment option.
Advanced Technical Innovation
The platform, protected by two key patents, offers several distinct scientific advantages:
Universal Application: Unlike traditional CAR-T therapies that target specific proteins, CytoMed's CAR can target multiple protein molecules expressed across various types of liquid and solid cancers, potentially expanding its therapeutic reach.
Streamlined Manufacturing: CytoMed has developed proprietary methods for expanding and modifying γδ T cells, enabling efficient production of clinical-grade cells at low cost.
Platform Integration: The technology enables the combination of antibodies, representing one of the latest advances in cancer treatment. Specifically, bispecific antibodies have been developed to enhance the T cells' cancer-fighting abilities while preserving their natural targeting mechanism.
Revolutionary IPSC-Derived Technology
A notable advancement in the platform is the development of iPSC-gdNKT cells, termed "Shogun Cells," in recognition of their Japanese Nobel Prize-winning origins. This innovative approach combines the benefits of induced pluripotent stem cells with the natural cancer-fighting abilities of gamma delta T cells, potentially offering a new paradigm in cell therapy.
Therapeutic Applications and Research Directions
The technology shows promise in treating both solid tumors and blood cancers. The platform's versatility enables integration with various therapeutic approaches, including:
- Chimeric antigen receptors
- Checkpoint inhibitors
- Bi-specific T cell engagers
- Antibody-drug conjugates
- Natural killer cells
Beyond oncology, CytoMed's research is exploring applications in:
- Autoimmune disorders
- Inflammatory conditions
- Regenerative medicine
Clinical Development and Future Directions
The ongoing ANGELICA trial represents a significant milestone as the first CAR T cell therapy trial by a Singapore biotech in Singapore. The trial aims to evaluate both safety and efficacy across multiple cancer types, including traditionally challenging solid tumors. This comprehensive approach not only examines the therapy's potential across different cancer stages but also demonstrates the platform's adaptability in addressing various cancer antigens while maintaining standardized production benefits, leading to affordability for many patients.
By combining the natural cancer-fighting abilities of gamma delta T cells with engineered enhancements, CytoMed provides a promising, inexpensive foundation for the future of cellular immunotherapy, potentially expanding treatment options for cancer patients. CytoMed benefits from its strategic location in Southeast Asia and low-cost infrastructure. It has successfully shipped frozen gamma delta T cells to international destinations with high cell viability and good results. The next action plan is to seek international trial collaborators for its unmodified gamma delta T cells to hasten clinical use.
Chairman & CEO Peter Choo commented, "Our bodies comprise trillions of cells all communicating with each other, so cellular medicine makes scientific logic. Our gamma delta T cell platform is very versatile and can be described metaphorically as an army of fresh, healthy soldiers who can be armed with different weapons such as chimeric antigen receptors and antibodies to fight various diseases including cancers."
