γδ T Cells: Bridging Innate and Adaptive Immunity for Next-Generation Cell Therapy

June 2025 — Taipei

γδ T cells represent a unique and powerful subset of T lymphocytes that combine features of both innate and adaptive immunity. Unlike the conventional αβ T cells that require antigen presentation via MHC molecules, γδ T cells recognize stress-induced ligands in an MHC-independent manner—making them highly effective against malignancies, infections, and even chronic inflammatory conditions. Despite accounting for only 1–5% of peripheral blood T cells, γδ T cells are now widely regarded as one of the most promising cell types for off-the-shelf, allogeneic immunotherapies.

The Biology of γδ T Cells

T cells are typically categorized based on their T cell receptor (TCR) heterodimer: most are αβ T cells, but a small fraction express γδ TCRs, including either Vγ9Vδ2 or Vδ1 chains. These γδ T cells can respond rapidly to stressed, infected, or transformed cells, often without requiring conventional antigen processing or presentation. Their quick reactivity and broad-spectrum cytotoxicity make them key immune sentinels and effectors.

Key mechanisms of tumor killing include:

• Direct lysis via natural cytotoxicity receptors and NKG2D ligands

• Secretion of perforin and granzymes

• TRAIL/FASL-induced apoptosis

• Antibody-dependent cellular cytotoxicity (ADCC)

• Antigen presentation to αβ T cells

• Activation of NK cells and B cells through 4-1BBL and cytokine release

Advantages of γδ T Cell-Based Therapy

Compared to traditional T cell therapies (e.g., CAR-T), γδ T cells offer several advantages:

1. MHC-independent recognition – Allows broad applicability across patients without the risk of graft-versus-host disease (GVHD).

2. Dual immune function – Combines innate immune speed with adaptive specificity.

3. Broad tumor targeting – Effective against both hematologic and solid tumors.

4. Non-genetically modified potency – Exhibits strong cytotoxicity without requiring genetic engineering.

5. Favorable safety profile – Clinical studies to date report minimal toxicity, with no evidence of cytokine release syndrome or neurotoxicity.

Applications in Oncology and Beyond

Cancer Immunotherapy

γδ T cells are under investigation for multiple tumor types, including triple-negative breast cancer, lung cancer, pancreatic cancer, hepatocellular carcinoma, renal cell carcinoma, and AML. Clinical studies have shown a correlation between γδ T cell infiltration and patient survival in breast and kidney cancers. The ability of γδ T cells to penetrate solid tumor microenvironments and exert cytotoxicity is particularly promising for difficult-to-treat cancers.

Infectious Diseases

These cells play a frontline role in fighting viral and bacterial infections (e.g., HBV, HCV, influenza, HIV) and are rapidly activated in the presence of microbial metabolites or host danger signals. γδ T cells can also eliminate infected or damaged cells, preventing further spread of infection.

Autoimmune and Inflammatory Conditions

Emerging research suggests that γδ T cells contribute to immune homeostasis and tissue repair. Their presence—or functional impairment—has been implicated in diseases such as lupus, rheumatoid arthritis, inflammatory bowel disease, and systemic myositis. Modulating γδ T cell activity may represent a novel approach to regulating pathogenic immune responses.

Anti-Aging and Regenerative Medicine

In the context of tissue regeneration, γδ T cells have been shown to promote healing by releasing growth factors like IGF-1. In wound models, they facilitate epithelial repair, particularly in skin and gut tissue. This positions them as a novel player in aging-related degeneration and chronic wound therapy.

Industry Landscape and Innovation

Globally, over a dozen biotechnology companies have entered the γδ T cell therapy field. Some pipelines integrate γδ T cells with chimeric antigen receptor (CAR) platforms, while others focus on unmodified, allogeneic γδ T cells. In April 2024, Hong Kong-based researchers pioneered the use of γδ T cell-derived exosomes in photodynamic therapy for melanoma—highlighting the potential for γδ T-based therapeutics to expand beyond traditional cell infusions into combination biologics and drug delivery systems.

JY BioMed’s Commitment

At JY BioMed, we are actively advancing γδ T cell-based platforms focused on the Vγ9Vδ2 subtype. Our pipeline spans multiple oncology indications, including glioblastoma, pancreatic cancer, and relapsed/refractory AML. We aim to provide fully integrated solutions—from antibody design and cell manufacturing to regulatory strategy and clinical development. Our approach is rooted in scientific rigor, regulatory compliance, and a vision to bring effective, accessible γδ T cell immunotherapies to patients worldwide.

Regulatory Disclaimer The γδ T cell therapies described herein are investigational products under preclinical or early clinical development. These therapies have not yet been approved by the U.S. FDA, Taiwan TFDA, or other global regulatory agencies. All development activities adhere strictly to international ethical guidelines and applicable regulatory frameworks.