Gamma delta T cell-based immunotherapies have emerged as a promising frontier in cancer treatment and beyond, building on the success of chimeric antigen receptor T-cell (CAR T cell) therapy and expanding on the potential of the immune system as a therapeutic modality. These unique T lymphocytes offer several advantages over conventional alpha beta T cells, including their ability to recognize a wide range of cellular stress signals without MHC restriction and reduced risk of graft vs. host disease (GvHD). As research progresses, gamma delta T cell therapies are showing potential not only in oncology but also in autoimmune and inflammatory conditions and viral disease, highlighting their versatility as a therapeutic approach.
The primary focus on gamma delta T cell therapies has been in oncology, particularly in hematological cancers like leukemia and lymphoma. One of the most advanced therapies in this field is OmnImmune (TCB-008), being developed by TC BioPharm, and currently in phase 2 clinical trials for acute myeloid leukemia (AML). OmnImmune is an unmodified allogeneic gamma delta T cell product, and preliminary studies have showed promising efficacy and safety profiles, providing hope to patients with relapsed or refractory AML who have few options for therapy. According to Neeraj Chawla, Research Head at Kuick Research, US and China are dominating the Global Gamma T Cell Therapies development landscape with more than 70% of therapies being developed at these two locations. Adding further, he also highlighted the fact that more than 30 therapies are under trials across the global.
The unique properties of gamma delta T cells have led researchers to investigate their potential in treating non-cancer indications, including autoimmune and inflammatory conditions and viral disease. In autoimmune and inflammatory conditions, gamma delta T cell therapies aim to modulate the immune response and restore balance, potentially offering novel approach to managing diseases like rheumatoid arthritis and multiple sclerosis. Notably, Adicet Bio is preparing to launch first-in-human clinical trials for its gamma delta T cell therapy candidate ADI-001 in lupus nephritis in June 2024, with recruitment yet to commence.
For viral infections, gamma delta T cells have shown promise in preclinical studies for their ability to recognize and eliminate virus-infected cell, sparking interest in their development for chronic viral infections and as a potential treatment for emerging viral threats. ImCheck Therapeutics, a France-based biotech company, is developing anti-Butyrophilin-3A (BTN3A) monoclonal antibodies to preferentially activate γ9Vδ2 T cells, a subset of gamma delta T cells, for battling infectious disorders. After becoming activated, these cells may coordinate a wide-ranging immune response via many channels, including granulocytes, CD8 T cells, and NK cells. These cells are useful in treating a variety of microbial diseases because they can fight off viral, bacterial/mycobacterial, and parasite infections.
Ongoing developments in the field of gamma delta T cell-based therapies are focused on enhancing their efficacy, persistence and manufacturability. For cell therapies, genetic engineering is being explored to improve gamma delta T cell function, such as introducing CARs or T cell receptors to enhance tumor targeting. Researchers are also investigating combination therapies, exploring the potential synergistic effects of combining gamma delta T cell therapies and antibodies with other immunotherapies, targeted therapies or conventional therapies.
As the field progresses, the success of CAR-T therapies has paved the way for increased interest and investment in gamma delta T cell-based approaches. The lessons learned from CAR-T development, including strategies for managing toxicities and improving persistence, are being employed to gamma delta T cell therapies, potentially accelerating their clinical development and eventual approval.
The future of gamma delta T cell-based immunotherapies looks promising, with potential applications extending beyond cancer treatment. As research continues and clinical data accumulates, these therapies may emerge as a popular tool in the fight against a range of challenging diseases. Their ability to bridge innate and adaptive immunity, combined with their unique recognition capabilities, positions gamma delta T cells as a versatile platform for immunotherapy development.
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