Natural γδT Cells
γδT cells are a unique subset of T cells found in the immune system. Unlike the more common αβ T cells, they don’t require MHC molecules to recognize danger signals. Instead, they can directly detect stress-induced molecules on the surface of infected or cancerous cells as part of the adaptive and innate immune system. This gives them several natural advantages:
- Fast response to tumors without prior sensitization.
- Ability to target a broad range of blood and solid cancers.
- Be manufactured from healthy donors and used as a ‘off-the-shelf’ treatment across different patients as an allogeneic approach.
- Low risk of triggering GVHDas allogeneic (donor-derived) based cellular therapies.
CAR- γδ T Cells: Supercharging the Immune Response
CAR (Chimeric Antigen Receptor) is a synthetic receptor artificially introduced into immune cells to redirect them to attack specific cancer targets, regardless of how the immune system normally recognizes threats.
When scientists engineer γδ T cells to express a CAR, they create CAR- γδ T cells, which combine the best of both worlds:
- The innate tumor-homing ability of γδ T cells.
- The precision targeting of a CAR against specific cancer markers (such as CD19, GD2, HER2, etc.).
- Recognize specific tumors more efficiently than natural γδ T cells.
- Kill specific cancer cells regardless of MHC status or immune evasion tactics.
Natural vs. CAR-Gamma-Delta T Cells
| Feature | Natural γδ T Cells | CAR-γδ T Cells |
| Tumor Recognition | Innate, broad (stress signals) | Engineered, highly specific (via CAR) |
| MHC Restriction | MHC-independent | MHC-independent |
| Antitumor Power | Moderate in some cases | Strong, enhanced killing ability of specific tumors |
| Allogeneic Use | Safe, low risk of GVHD | Safe, low risk of GVHD |
| Modification in Lab | None | Modified via engineering protocols |
| Target Range | Broad, less defined | Specific and programmable |
While natural γδ T cells are powerful by design, CAR- γδ T cells represent a major leap forward in immunotherapy. By combining nature’s flexibility with scientific precision, they hold exciting promise for next-generation cancer treatments—especially in patients whose tumors are resistant to traditional therapies.
Collaboration with CytoMed Therapeutics
We are proud to collaborate with CytoMed Therapeutics Limited (NASDAQ: GDTC), a pioneering clinical-stage biopharmaceutical company headquartered in Singapore. Spun off from Singapore’s leading public research institution, the Agency for Science, Technology and Research (A*STAR), CytoMed is focused on developing innovative, affordable, and donor-derived allogeneic cell-based immunotherapies to treat a broad range of cancers.
https://www.globenewswire.com/news-release/2025/04/28/3069638/0/en/CytoMed-Therapeutics-Reports-Full-Year-Ended-December-31-2024-Financial-Results-and-Provides-Clinical-and-Corporate-Updates.html
https://csimarket.com/news/cytomed-therapeutics-makes-strides-in-cancer-treatment-with-innovative-car-t-cell-therapy-and-strategic-expansion-int2024-10-07112083
CytoMed’s Breakthrough Technologies
CytoMed’s research centers on the use of gamma-delta (γδ) T cells and natural killer (NK) cells, both of which offer powerful anti-tumor activity with reduced risk of graft-versus-host disease (GVHD). These cells are ideal for off-the-shelf therapies that do not require patient-specific customization, making them scalable and cost-effective.
Key therapeutic programs include:
- CTM-N2D Therapy: CAR-γδ T cells targeting NKG2D ligands that are stress-induced molecules commonly expressed on cancer cells. This therapy offers a ready-to-use treatment that bypasses the need for individualized cell harvesting (autologous).
- CTM-GDT Therapy: Donor-derived, unmodified γδ T cells expanded to harness their natural cytotoxicity against a variety of cancer types.
- gdNKT Therapy: iPSC-derived γδ NKT cells, combining the strengths of both γδ T cells and NK cells to create a potent and scalable cell-based cancer immunotherapy.
Advancing Cancer Immunotherapy
In 2023, CytoMed initiated its first-in-human Phase I clinical trial (ANGELICA study), approved by Singapore’s Health Sciences Authority (HSA), to evaluate the safety and effectiveness of its CAR-γδ T cell therapy in both blood and solid tumors.
Additionally, CytoMed entered into a strategic research collaboration with India’s SunAct Cancer Institute, aiming to launch a Phase II clinical trial targeting solid tumors using allogeneic γδ T cells.
Superior Manufacturing and Safety
CytoMed operates a GMP-certified facility and has developed proprietary methods for expanding γδ T cells from donor blood, ensuring consistency, safety, and scalability. Unlike conventional CAR-T therapies that rely on patient blood cells (autologous) and complex processing, CytoMed’s CAR-γδ T cells are:
- Derived from healthy donors
- Manufactured via simple blood draws and streamlined protocols
- Modified using mRNA electroporation, which lowers the risk of insertional mutagenesis and long-term adverse effects
This collaboration represents a significant step forward in making next-generation cancer therapies safer, more accessible, and more effective. CytoMed’s approach allows us to contribute to advancing cell-based immunotherapy beyond traditional limitations, particularly in solid tumors, where treatment options remain limited.
Together with CytoMed Therapeutics, we aim to bring promising, science-driven therapies to patients who need them most.
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CAR-γδ T Cell
Manufacturing CAR-γδ T Cells (Graphic)
Unlike the conventional chimeric antigen receptor (CAR) -T cell technology that relies on the use of patient blood cells (autologous) to generate highly personalized αβ T cell-based therapy for certain cancers, our CAR-γδ T cell technology utilizes healthy donor blood cells to manufacture the “off-the-shelf” CTM-N2D therapy targeting stress-induced cancer antigens that is suitable for many patients across a wide spectrum of cancers.
Manufacturing CAR-γδ T Cells (Graphic)
CytoMed’s CAR-γδ T Cells vs Conventional CAR-T Cells:
Technology, Manufacture and Implications
| TECHNOLOGY | CONVENTIONAL CAR-T CELLS | CYTOMED’SCAR-γδ TCELLS |
| Application setting | Autologous use, applicable to a single patient only | Allogeneic use, applicable to many patients |
| Industrial implication | Highly personalized “made-to-order” product, expensive | “Off-the-shelf” product, affordable |
| Source of starting material | Patient blood cells, potential issues include:
|
Healthy donor blood cells, advantages include:
|
| Collection of starting material | Invasive leukapheresis to collect immune cells | Simple blood draw to collect blood sample |
| Manufacturing process | A complicated manufacturing process includes:
|
A simple manufacturing process includes:
|
| Method to install CAR | Lentivirus, potential issues include:
|
mRNA electroporation, advantages include:
|
| Target antigen | Lineage-specific antigen(e.g. CD19), which expresses in both malignant cells and normal cells and cause “on-target off-cancer” side effect. | Stress-induced antigens (e.g. NKG2DLs and phosphoantigen), which mainly express on cancer cells and reduce the risk of “on-target off-cancer” side effect. |
| Finished product | CAR-grafted αβ T cells | CAR-grafted γδ T cells |
| Indication | For haematological malignancies so far | For solid tumors and haematological malignancies |
| Industrial implication | Highly personalized “made-to-order” product, expensive | “Off-the-shelf” product, affordable |
