Insufficiency of compound immune checkpoint blockade to overcome engineered T cell exhaustion in pancreatic cancer.

ABSTRACT:

Background

Achieving robust responses with adoptive cell therapy for the treatment of the highly lethal pancreatic ductal adenocarcinoma (PDA) has been elusive. We previously showed that T cells engineered to express a mesothelin-specific T cell receptor (TCR_Msln) accumulate in autochthonous PDA, mediate therapeutic antitumor activity, but fail to eradicate tumors in part due to acquisition of a dysfunctional exhausted T cell state.

Methods

Here, we investigated the role of immune checkpoints in mediating TCR engineered T cell dysfunction in a genetically engineered PDA mouse model. The fate of engineered T cells that were either deficient in PD-1, or transferred concurrent with antibodies blocking PD-L1 and/or additional immune checkpoints, were tracked to evalua

SUBMITTER: Stromnes IM 

PROVIDER: S-EPMC8883283 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature