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Article Dans Une Revue European Journal of Immunology Année : 2024

Camelid‐derived T cell engagers harnessing human γδ T cells as promising antitumor immunotherapeutic agents

Résumé

In the last decade, there has been a surge in developing immunotherapies to enhance the immune system's ability to eliminate tumor cells. Bispecific antibodies known as T cell engagers (TCEs) present an attractive strategy in this pursuit. TCEs aim to guide cytotoxic T cells toward tumor cells, thereby inducing a strong activation and subsequent tumor cell lysis. In this study, we investigated the activity of different TCEs on both conventional alpha‐beta (αβ) T cells and unconventional gamma delta (γδ) T cells. TCEs were built using camelid single‐domain antibodies (VHHs) targeting the tumor‐associated antigen CEACAM5 (CEA), together with T cell receptor chains or a CD3 domain. We show that Vγ9Vδ2 T cells display stronger in vitro antitumor activity than αβ T cells when stimulated with a CD3xCEA TCE. Furthermore, restricting the activation of fresh human peripheral T cells to Vγ9Vδ2 T cells limited the production of protumor factors and proinflammatory cytokines, commonly associated with toxicity in patients. Taken together, our findings provide further insights that γδ T cell‐specific TCEs hold promise as specific, effective, and potentially safe molecules to improve antitumor immunotherapies.
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Dates et versions

hal-04591412 , version 1 (28-05-2024)

Identifiants

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Lola Boutin, Clement Barjon, Morgane Chauvet, Laura Lafrance, Eric Senechal, et al.. Camelid‐derived T cell engagers harnessing human γδ T cells as promising antitumor immunotherapeutic agents. European Journal of Immunology, In press, ⟨10.1002/eji.202350773⟩. ⟨hal-04591412⟩
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