T-cell receptor beta variable 6 and 10 positive CD8+ T cells (Vβ6/Vβ10+ CD8+ T cells)

Vβ6/Vβ10+ CD8+ T cells are a specific subset of cytotoxic T lymphocytes defined by the expression of the Vβ6 or Vβ10 variable regions of the T-cell receptor (TCR) beta chain [1, 4]. These cells are a primary focus of novel Selective T Cell Activation and Reprogramming (STAR) therapies, which aim to selectively expand and activate these subsets to treat advanced solid tumors [5, 6]. Unlike traditional immunotherapies that target all T cells or specific antigens, these therapies use bifunctional molecules like invikafusp alfa (STAR0602) to bind the germline-encoded Vβ6/Vβ10 regions and provide co-stimulation via IL-2 in cis [1, 3]. This interaction induces a non-clonal mode of activation, bypassing the need for specific MHC-peptide recognition and promoting the expansion of T cells with an atypical central memory phenotype [2, 4]. These expanded cells exhibit enhanced anti-tumor activity and can overcome resistance to programmed cell death-1 (PD-1) inhibitors in immunologically cold tumors [5, 6]. Clinical trials have demonstrated that targeting this subset can lead to significant tumor shrinkage and a manageable safety profile in patients with high tumor mutational burden or microsatellite instability [2, 5].

Other names

Vβ6+ CD8+ T cellsVβ10+ CD8+ T cellsTCR Vβ6/Vβ10+ CD8+ T cellsVβ6/Vβ10-expressing CD8+ T cellsInvikafusp alfa target cells

Selective activation and expansion of Vβ6/Vβ10 T-cell subsets via a bifunctional antibody-fusion molecule that engages a non-clonal mode of TCR activation and IL-2 receptor co-stimulation in cis.