Tumor blood vessel and melanoma-associated antigen peptide-MHC complexes (TBVA/MAA-pMHC)

This target represents a composite of HLA-A2-restricted peptide-MHC complexes derived from both tumor blood vessel antigens (TBVAs) and melanoma-associated antigens (MAAs). The specific antigens included are Ephrin type-A receptor 2 (EphA2), Hemoglobin subunit beta (HBB), Neuropilin-1 (NRP1), Regulator of G protein signaling 5 (RGS5), and Tumor endothelial marker 1 (TEM1/CD248). These antigens are presented on autologous type-1 polarized dendritic cells (alphaDC1) to stimulate a robust CD8+ T-cell mediated immune response. By targeting both the malignant melanoma cells and the tumor-associated vascular endothelium, this strategy aims to disrupt the tumor's nutrient supply while simultaneously inducing direct tumor cell lysis. This multi-antigen approach is designed to overcome tumor heterogeneity and prevent immune escape by targeting the relatively stable tumor microenvironment.

Other names

Tumor blood vessel antigens (TBVA)Melanoma-associated antigens (MAA)Type-1 polarized dendritic cell (alphaDC1) vaccine targetsEphA2/HBB/NRP1/RGS5/TEM1 multi-antigen complex

The therapeutic approach involves the administration of autologous type-1 polarized dendritic cells (alphaDC1) pulsed with HLA-A2-restricted peptides derived from tumor blood vessel antigens (EphA2, HBB, NRP1, RGS5, TEM1) and melanoma-associated antigens. These dendritic cells present the peptide-MHC complexes to endogenous CD8+ T-cells, priming and expanding a cytotoxic T-lymphocyte (CTL) response that targets both the tumor cells and the supporting tumor vasculature.