Naturally occurring T cell mutations enhance engineered T cell therapies.

ABSTRACT: Adoptive T cell therapies have produced exceptional responses in a subset of patients with cancer. However, therapeutic efficacy can be hindered by poor T cell persistence and function¹. In human T cell cancers, evolution of the disease positively selects for mutations that improve fitness of T cells in challenging situations analogous to those faced by therapeutic T cells. Therefore, we reasoned that these mutations could be co-opted to improve T cell therapies. Here we systematically screened the effects of 71 mutations from T cell neoplasms on T cell signalling, cytokine production and in vivo persistence in tumours. We identify a gene fusion, CARD11-PIK3R3, found in a CD4⁺ cutaneous T cell lymphoma², that augments CARD11-BCL10-MALT1 complex signalling a

SUBMITTER: Garcia J 

PROVIDER: S-EPMC11573425 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature