Multiple Myeloma-associated multi-peptide antigen complex (XBP1, CD138, CS1) presented on HLA-A2 (PVX-410)

This target consists of a specific combination of four HLA-A*02:01-restricted immunogenic peptides derived from three proteins highly overexpressed in multiple myeloma: X-box binding protein 1 (XBP1), Syndecan-1 (CD138), and SLAM family member 7 (CS1/SLAMF7). The specific epitopes include XBP1 unspliced (US184-192), XBP1 spliced (SP367-375), CD138 (260-268), and CS1 (239-247). These peptides are presented by the Major Histocompatibility Complex (MHC) Class I molecule HLA-A2 on the surface of malignant plasma cells. In the context of immunotherapy, particularly the PVX-410 vaccine, these peptides act as targets to stimulate a robust, tumor-specific cytotoxic T lymphocyte (CTL) response. XBP1 is a key transcription factor in the unfolded protein response essential for plasma cell differentiation, while CD138 and CS1 are surface markers critical for myeloma cell adhesion and survival. By targeting multiple antigens simultaneously, this approach aims to overcome tumor heterogeneity and prevent immune escape. Clinical development has focused on using these peptides to treat smoldering multiple myeloma to delay progression to active disease, often in combination with immune checkpoint inhibitors like durvalumab or immunomodulatory drugs like lenalidomide.

Other names

XBP1/CD138/CS1 multi-peptide vaccinePVX-410 peptidesXBP-1 US184-192 / XBP-1 SP367-375 / CD138 260-268 / CS1 239-247Multi-peptide myeloma vaccine

Induction of peptide-specific CD8+ cytotoxic T lymphocytes (CTLs) that recognize and lyse HLA-A2+ plasma cells expressing XBP1, CD138, and CS1.