Immunotherapeutic 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.
Keywords: Antigen-specific immunotherapy; Artificial antigen-presenting system; Costimulation; Peptide-MHC complex.
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