Tonic 4-1BB Costimulation in Chimeric Antigen Receptors Impedes T Cell Survival and Is Vector-Dependent

Tonic 4-1BB Costimulation in Chimeric Antigen Receptors Impedes T Cell Survival and Is Vector-Dependent.

Antigen-independent tonic signaling by chimeric antigen receptors (CARs) can increase differentiation and exhaustion of T cells, limiting their potency. Incorporating 4-1BB costimulation in CARs may enable T cells to resist this functional exhaustion; however, the potential ramifications of tonic 4-1BB signaling in CAR T cells remain unclear. Here, we found that tonic CAR-derived 4-1BB signalin...

T Cell Survival Memory Promotes Antigen-Independent CD8 IL-15-Dependent Induction of 4-1BB

Modulation of cord blood CD8+ T-cell effector differentiation by TGF-beta1 and 4-1BB costimulation.

Transforming growth factor-beta1 (TGF-beta1), an immunosuppressive cytokine, inhibits cytotoxic T cell (CTL) immune responses. In contrast, 4-1BB (CD137), a costimulatory molecule in the tumor necrosis factor (TNF) receptor family, amplifies CTL-mediated antitumor immune responses. We investigated whether TGF-beta1 responses could be reversed by 4-1BB costimulation during in vitro differentiati...

Enhancing CAR T cell persistence through ICOS and 4-1BB costimulation.

Successful tumor eradication by chimeric antigen receptor-expressing (CAR-expressing) T lymphocytes depends on CAR T cell persistence and effector function. We hypothesized that CD4+ and CD8+ T cells may exhibit distinct persistence and effector phenotypes, depending on the identity of specific intracellular signaling domains (ICDs) used to generate the CAR. First, we demonstrate that the ICOS ...

Modulation of cord blood CD8 T-cell effector differentiation by TGF- 1 and 4-1BB costimulation

Transforming growth factor1 (TGF1), an immunosuppressive cytokine, inhibits cytotoxic T cell (CTL) immune responses. In contrast, 4-1BB (CD137), a costimulatory molecule in the tumor necrosis factor (TNF) receptor family, amplifies CTLmediated antitumor immune responses. We investigated whether TGF1 responses could be reversed by 4-1BB costimulation during in vitro differentiation of naive CD8 ...