Targeting the Cancer Mutanome
Tuesday, August 30, 2016 | 6:30-9:00
Emerging sequencing and bioinformatics technologies are now giving researchers new perspectives on the mutations in patient specific antigens, now collectively known as the cancer mutanome. Our dinner short course offers academic and industry perspectives on the analytical and computational methods used to identify neo-epitopes within a mutanome that are candidates for therapeutic intervention – and the potential applications of this knowledge in patient diagnostics and immunotherapy. An open discussion format will allow those working in this space to share insights and experiences on how to advance this new field into clinical practice.
Overview and Course Introduction
Laszlo Radvanyi, Ph.D., Senior Vice President; Head of Immuno-Oncology Translational Innovation Platform (TIP), EMD Serono
Identification of TNBC-Specific Neoantigens from TILs Expanded in the Presence of a 4-1BB Agonistic Antibody
Luis M. Vence, Ph.D., Scientific Manager, Immunology, MD Anderson Cancer Center
TILs from TNBC tissue can be grown and we determined that the use of 4-1BB agonistic antibody to generate TIL increases total yield of TIL, CD8+ T cell frequency, CD8+ T cell cytotoxicity and does not affect TCR Vα or Vβ spectrotyping. In the expanded TILs we were able to detect CD8 T cells that recognized tumor-specific neoantigens but not their wt form. These neoantigens were identified in two different patients.
Identification and Isolation of Neoantigen-Specific Lymphocytes in Peripheral Blood of Cancer Patients
Alena Gros Vidal, Ph.D., Principal Investigator, Tumor Immunology and Immunotherapy, Vall d’Hebron Institute of Oncology (VHIO), Spain
Neoantigen-specific CD8+ and CD4+ lymphocytes can frequently be detected infiltrating tumors, but only rare clonotypes have been identified and isolated from the blood using HLA multimers, or through successive rounds of in vitro sensitization. Our work demonstrates that selection of circulating CD8+PD-1+ cells can identify the diverse repertoire of neoantigen-reactive CD8+ lymphocytes in melanoma patients and provides an alternative strategy to study and potentially exploit these reactivities therapeutically.
Identification of Neoantigen Candidates from a Mutanome
Suchit Jhunjhunwala, Ph.D., Scientist, Bioinformatics & Computational Biology, Genentech
Identification of neoantigens from the mutanome is the first step for any personalized cancer vaccine. Typical tumors can harbor tens to hundreds of coding mutations, but a small fraction of mutations can generate neoantigens presented by MHC class I molecules. I will talk about several bioinformatics methods that are used for narrowing down to candidate neoantigens from mutation data, their limitations and give a perspective of where future efforts will focus in this space.