Abstract
Pancreatic ductal adenocarcinomas (PDAs) erect physical barriers to chemotherapy and induce multiple mechanisms of immune suppression, creating a sanctuary for unimpeded growth. We tested the ability of T cells engineered to express an affinity-enhanced T cell receptor (TCR) against a native antigen to overcome these barriers in a genetically engineered model of autochthonous PDA. Engineered T cells preferentially accumulate in PDA and induce tumor cell death and stromal remodeling. However, tumor-infiltrating T cells become progressively dysfunctional, a limitation successfully overcome by serial T cell infusions that resulted in a near-doubling of survival without overt toxicities. Similarly engineered human T cells lyse PDA cells in vitro, further supporting clinical advancement of this TCR-based strategy for the treatment of PDA.
Original language | English (US) |
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Pages (from-to) | 638-652 |
Number of pages | 15 |
Journal | Cancer Cell |
Volume | 28 |
Issue number | 5 |
DOIs | |
State | Published - Nov 9 2015 |
Bibliographical note
Publisher Copyright:© 2015 Elsevier Inc.