Only a small percentage of the changes that arise within a cancerous cell can be directly targeted by the human immune system – most neoplastic changes are not “visible” for antibody targeting at the plasma membrane.  It is the human major histocompatibility complex class I molecules, or human leukocyte antigens (HLA), that transport peptide fragments of tumor antigens to the surface of the cancerous cell, thereby allowing T lymphocytes to review the entirety of the intracellular protein content of a tumor cell.  HLA molecules sample peptides derived from (1) tumor specific oncogenes, (2) mutated tumor suppressor genes, (3) aberrantly expressed oncofetal proteins, and (4) tumor related proteins. HLA molecules present these tumor-specific peptides at the cell surface. 

Pure MHC has a combined expertise in immune proteomics and HLA biology, and here we describe use of Pure MHC’s proprietary Peptide HLA Immunotherapy Data Resource (PHIDR) healthy tissue HLA database to de-risk the development of TCR, TCR mimetics, and T cell eliciting immune therapies.  We first describe how our immune therapy partners access the PHIDR healthy tissue database, assessing the frequency and abundance of their selected HLA/peptide targets on healthy human organs and tissues.  Next, we describe the Pure MHC approach for identifying HLA/peptide complexes on primary tumor tissues and the subtractive use of the PHIDR healthy tissue database to provide a select list of HLA/peptide complexes that are found only on tumors.  The frequency and abundance of HLA/peptide targets on tumors, their absence from healthy tissues, and the promise that carefully selected tumor specific HLA peptide complexes offer to the architects of immune therapies are discussed.