Sisi Sarkizova, Michael Rooney
Hacohen Lab, Broad / MGH; Neon Thereapeutics
Improving the rules of endogenous antigen prediction to support personalized cancer vaccine development
Abstract: In the seminar, we will see how tumor-specific mutations (neo-antigens) can stimulate the immune recognition of cancer cells and be used as a therapeutic strategy. For such strategy to be successful, we need to be able to predict which endogenous peptide antigens will be presented on the cell surface by polymorphic HLA class I gene variants. We will present analyses of our single HLA peptide data which allowed us to develop improved rules for endogenous peptide presentation based on the physicochemical properties of binding peptides, patterns of peptide cleavage and abundance of cognate transcripts. Incorporating these findings into neural network models improved prediction of endogenous peptide binding as compared to current predictive algorithms. We will end by reviewing very encouraging results from a tumor vaccine trial in melanoma patients.
Primer: Tumor immunity
Abstract: In the primer, we will introduce the basics of how the adaptive immune system recognizes diseased cells and see that immune responses rely on the ability of cytotoxic T cells to identify and eliminate cells that display disease-associated antigens bound to specific cell-surface receptors (the human leukocyte antigen (HLA) class I molecules). We will discuss how this mechanism extends to cancer, what are some strategies by which tumors evade immune detection, and what are the therapeutic interventions that can boost immune clearance of tumors.