TIM-3, LAG-3, or 2B4 gene disruptions increase the anti-tumor response of engineered T cells.

ABSTRACT:

Background

In adoptive T cell therapy, the long term therapeutic benefits in patients treated with engineered tumor specific T cells are limited by the lack of long term persistence of the infused cellular products and by the immunosuppressive mechanisms active in the tumor microenvironment. Exhausted T cells infiltrating the tumor are characterized by loss of effector functions triggered by multiple inhibitory receptors (IRs). In patients, IR blockade reverts T cell exhaustion but has low selectivity, potentially unleashing autoreactive clones and resulting in clinical autoimmune side effects. Furthermore, loss of long term protective immunity in cell therapy has been ascribed to the effector memory phenotype of the infused cells.

Methods

We simultaneously redirected T cell

SUBMITTER: Cianciotti BC 

PROVIDER: S-EPMC10953820 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature