Development of Novel CD138 Antigen-Specific Peptide Capable of Eliciting Myeloma-Specific Cytotoxic T Lymphocytes Response.

Multiple myeloma (MM) is characterized by the accumulation of mature plasma cells in the bone marrow. Despite progress in treatment, the disease still remains incurable, therefore novel therapeutic approaches are required to achieve better treatment. Development of peptide-based immunotherapies against specific tumor-associated antigens offers an attractive approach that may lead to tumor-targeted cellular therapy in MM patients. CD138 (Syndecan-1) is an unique target expressed on the surface of MM cells and normal plasma cells with very limited other distribution or expression. CD138 has been reported to play an important role in myeloma cell survival and, infact, is used to purify MM cells in laboratory experiments. The purpose of this study was to develop immunogenic peptides derived from CD138 antigen for the induction of antigen-specific cytotoxic T lymphocytes (CTLs) against MM. We have identified an immunogeneic HLA-A2-specific CD138 peptide that is capable of inducing MM specific-CTLs. To induce the specific CTLs, HLA-A2-positive normal human T lymphocytes were stimulated with autologous dendritic cells or T2 cells pulsed with the CD138 peptide. The generated CTLs showed a distinct phenotype consisting of 67% of CD69⁺/CD45RO⁺ and 1% of CD45RA⁺/CCR7⁺ T cells, characteristic of effector memory cell population. A significant (p < 0.05) increase in T cell proliferation and IFN-g secretion were observed by the CTLs following restimulation with HLA-A2⁺/CD138⁺ MM cells. The CTLs displayed HLA-A2-restricted CD138-specific cytotoxic activity against MM cell, demonstrated as 76% and 86% cytotoxicity at Effector:Target ratios of 20:1 or 60:1, respectively. The MM cell-specific cytotoxicity was confirmed in “cold” target inhibition assays using HLA-A2.1⁺/CD138⁺ MM cells as “cold” inhibitor, demonstrated 25% and 39% reduction in cytotoxicity when incubated with cold inhibitors at E:T ratios of 20:1 or 60:1, respectively. A distinct CD138 peptide-specific tetramer⁺/CD8⁺ population was also confirmed. Taken together, these data demonstrate the efficacy of the immunogenic CD138 peptide in inducing a cellular immune response in MM for future clinical application.