T-cell receptor beta variable 6 and 10 (TRBV6/TRBV10)

Vβ6/Vβ10+ CD4+ T cells are a specific subset of helper T cells defined by the expression of the variable beta 6 (TRBV6) or variable beta 10 (TRBV10) chains in their T-cell receptor (TCR) complex (Hsu et al., 2023). These subsets represent approximately 6-10% of the total T-cell repertoire in humans and are frequently found among tumor-infiltrating lymphocytes (TILs) in various solid malignancies (Sullivan et al., 2023). Because these TCR chains are germline-encoded, they provide a unique handle for the selective, non-clonal activation of a significant portion of the immune system without the need for patient-specific antigen identification (Marengo Therapeutics, 2024). Therapeutically, this target is addressed by novel bifunctional molecules like invikafusp alfa (STAR0602), which consists of an anti-Vβ6/Vβ10 antibody fused to a native interleukin-2 (IL-2) cytokine (Hsu et al., 2023). By binding the TCR and the IL-2 receptor simultaneously on the same cell, these agents drive the selective expansion of Vβ6/Vβ10+ CD4+ and CD8+ T cells into a central memory-like state (Hsu et al., 2023). This mechanism is designed to boost antitumor immunity and increase TCR repertoire diversity while avoiding the severe systemic toxicities and regulatory T-cell expansion typically associated with high-dose IL-2 or pan-T-cell activators (Sullivan et al., 2023).

Other names

Vβ6/Vβ10 T-cell receptorV-beta 6 and V-beta 10 T-cell receptorTRBV6TRBV10T-cell receptor beta variable 6T-cell receptor beta variable 10

Selective T-cell receptor (TCR) agonism and cis-targeted interleukin-2 (IL-2) receptor activation to promote T-cell expansion (Hsu et al., 2023).