A novel immunogenic CS1-specific peptide inducing antigen-specific cytotoxic T lymphocytes targeting multiple myeloma.

The CS1 antigen provides a unique target for the development of an immunotherapeutic strategy to treat patients with multiple myeloma ( MM). This study aimed to identify HLA- A2+ immunogenic peptides from the CS1 antigen, which induce peptide-specific cytotoxic T lymphocytes ( CTL) against HLA- A2+ MM cells. We identified a novel immunogenic HLA- A2-specific CS1239-247 ( SLFVLGLFL) peptide, which induced CS1-specific CTL ( CS1- CTL) to MM cells. The CS1- CTL showed a distinct phenotype, with an increased percentage of effector memory and activated CTL and a decreased percentage of naïve CTL. CS1239-247 peptide-specific CD8+ T cells were detected by Dimer X analyses and demonstrated functional activities specific to the peptide. The CTL displayed HLA-A2-restricted and antigen-specific cytotoxicity, proliferation, degranulation and γ-interferon ( IFN-γ) production against both primary MM cells and MM cell lines. In addition, the effector memory cells subset ( CD45 RO+ CCR7−/ CD3+ CD8+) within CS1- CTL showed a higher level of CD107a degranulation and IFN-γ production as compared to effector cells ( CD45 RO− CCR7−/ CD3+ CD8+) against HLA- A2+ primary MM cells or MM cell lines. In conclusion, this study introduced a novel immunogenic HLA- A2-specific CS1239-247 peptide capable of inducing antigen-specific CTL against MM cells that will provide a framework for its application as a novel MM immunotherapy. [ABSTRACT FROM AUTHOR]