Video On Demand:
Unbiased Functional Identification and Therapeutic Targeting of Tumor Neoantigens
Stephen Schoenberger, Ph.D, Center Head; Professor, La Jolla Institute of Immunology
Neoantigens (NeoAg) offer attractive therapeutic targets for directing a patient’s immune response to the immunogenic subset of mutations expressed by their cancer cells. Despite the specificity with which NeoAg can enable tumor recognition, the majority of approaches for their identification rely on purely predictive methods based on a patient’s HLA binding which have met with limited success in revealing natural targets present on tumor cells, with less than 3% of selected mutations recognized as T cell targets. We have developed a novel HLA-agnostic platform which combines genomic sequencing with bioinformatics to nominate a subset of mutations for subsequent functional T cell analysis using autologous PBMC to verify, rather than predict, patient-specific NeoAg. Using this approach, we find that >35% of mutations selected by our algorithm can be verified as neoantigens in low mutational burden (TMB) tumors by CD4+ and CD8+ T cells recognizing common activating mutations in driver oncogenes and numerous patient-specific “passenger” mutations, We have additionally established a single-cell sequencing platform for isolation of genes encoding T cell receptors (TCRs) which mediate recognition of shared NeoAg in driver and viral oncogenes as well as a patient-derived xenograft (PDX) cell line system through which their in vivo efficacy in tumor eradication can be evaluated.
Stephen Schoenberger, Ph.D.
Dr. Schoenberger received his B.S. from the University of California, Los Angeles in 1987 and his Ph.D. from the same university in 1992. In 1993, Dr. Schoenberger was a Postdoctoral Fellow in Immunohematology at the University of Leiden Hospital, the Netherlands, from 1993-1998. Dr. Schoenberger is a member of numerous grant review panels and a reviewer for many scientific publications. He is also a member of the editorial advisory board for the Journal of Experimental Medicine.