Human leukocyte antigen A*02:01-peptide complex (DPX-0907) (HLA-A*02:01/DPX-0907)

The target is the molecular complex consisting of the Human Leukocyte Antigen (HLA) allele A*02:01 and seven specific tumor-associated antigen (TAA) peptides (Berinstein et al., 2012). HLA-A*02:01 is a Major Histocompatibility Complex (MHC) Class I molecule that plays a critical role in the immune system by presenting intracellularly derived peptides to CD8+ cytotoxic T-cells (UniProt P04439). The DPX-0907 vaccine, developed using the DepoVax platform, delivers seven HLA-A2-restricted peptides—MAGE-A1, MAGE-A3, NY-ESO-1, PRAME, Survivin, Melan-A, and Tyrosinase—which are presented within the HLA-A*02:01 peptide-binding groove (Berinstein et al., 2012). This presentation is essential for the activation and expansion of polyfunctional T-cells that can recognize and eliminate tumor cells expressing these antigens (FiercePharma, 2012). Clinical trials have demonstrated that this target is relevant for HLA-A2-positive patients with breast, ovarian, or prostate cancers, where these antigens are frequently overexpressed (Journal of Translational Medicine, 2012). While DPX-0907 showed promising immunogenicity in Phase I trials, the therapeutic challenge remains the potential for tumor immune escape through the downregulation of HLA molecules or antigen loss.

Other names

HLA-A*02:01 peptide-binding groove presenting DPX-0907 tumor-associated antigen peptidesHLA-A2-restricted tumor-associated antigen complexMHC Class I-peptide complex (DPX-0907)HLA-A*02:01-restricted TAA complex

Induction of antigen-specific CD8+ T-cell responses through the presentation of tumor-associated antigen peptides by HLA-A*02:01 molecules to T-cell receptors.