Activation and differentiation of cognate T cells by a dextran‐based antigen‐presenting system for cancer immunotherapy

Abstract

AbstractImmunotherapeutic modulation of antigen‐specific T‐cell responses instead of the whole repertoire helps avoid immune‐related adverse events. We have developed an artificial antigen‐presenting system (aAPS) where multiple copies of a multimeric peptide‐MHC class I complex presenting a murine class I MHC restricted ovalbumin‐derived peptide (signal 1), along with a costimulatory ligand (signal 2) are chemically conjugated to a dextran backbone. Cognate naive CD8+ T cells, when treated with this aAPS underwent significant expansion and showed an activated phenotype. Furthermore, elevated expression of effector cytokines led to the differentiation of these cells to cytotoxic T lymphocytes which resulted in target cell lysis, indicative of the functional efficacy of the aAPS. CD8+ T cells with decreased proliferative potential due to repeated antigenic stimulation could also be re‐expanded by the developed aAPS. Thus, the developed aAPS warrants further engineering for future application as a rapidly customizable personalized immunotherapeutic agent, incorporating patient‐specific MHC‐restricted tumor antigens and different costimulatory signals to modulate both naive and antigen‐experienced but exhausted tumor‐specific T cells in cancer.