Tumor & Cancer Immunology and Immunotherapy

Biography

Biography: Marc Delcommenne

Abstract

Rapid discovery and identification of many new and novel tumor associated epitopes and neoantigens can potentially result in potent cancer vaccines. However, no verdict of immunogenicity may be made without a rapid method to measure the binding of these peptides to MHC of the hosts.   While existing methodologies rely on UV cleavage of exiting peptide on monomeric MHC complexes and a subsequent lengthy tetramerization procedure, the platform presented here produces tetramers ready for cell staining to detect antigen-specific T cells in just four hours.  We have devised a fast and user-friendly peptide exchange tetramer platform (also referred as QuickSwitch™ Quant) that can both help determine binding of novel peptides, including neoantigens, to MHC class I molecules and generate new specificity MHC class I tetramers for peptide specific T cell detection.  We have developed a platform / kit for the generation of new specificity MHC tetramers, whereby a peptide of interest and a peptide exchange factor is incubated with a fluorescently labeled tetramer containing a special exiting peptide.  This study aimed to determine whether the peptide exchange HLA-A*02:01 tetramer platform can be used for evaluating the biological activity of a vaccine.  The tested vaccine was DPX-Survivac, an ovarian cancer vaccine candidate which consists of several survivin peptide antigens that are each restricted to a different human class I allele. We evaluated the specificity and sensitivity of the platform for assessing the biological activity of SurA2.M, an HLA-A2-restricted peptide, in DPX-Survivac.  We tested the detection of the peptide prepared individually in a buffered solution or in the DPX-Survivac vaccine prepared in an aqueous formulation.  Results indicate that peptide exchange rate of SurA2.M is similar whether it is dissolved individually in a buffered solution or in a matrix of the vaccine.  Thus, by optimizing a concentration curve using individual peptides, the peptide exchange tetramer platform can be used to examine the binding of peptide vaccines in a mixture and to quantify the concentration of HLA-A2 restricted peptides in simple solutions or more complex formulations.