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Impact

I use in silico, in vitro and in vivo approaches to ask fundamental questions about cancer biology. My doctoral work was motivated by trying to understand how self/non-self discrimination occurs in the context of a tumor. I developed a novel approach to link MHC-I neoantigen expression to cellular barcodes called “PresentER” (Gejman eLife 2018; Gejman, Ca. Imm. Res. 2020). “PresentER” allows the creation of libraries of tens of thousands of precisely defined neoantigens to study TCR-reactivity and immunogenicity. Using PresentER libraries, we discovered that clonally expressed neoantigens could elicit strong immune responses in immunocompetent mice that eliminated tumors, while neoantigens with low clonality or in competition with other neoantigens could not. This may explain the clinically important inverse relationship between degree of intratumoral heterogeneity and response to immunotherapy in patients with cancer. We have also used this system to study the target-specificity of T cell receptor-based therapeutics and unexpectedly revealed extensive off-targets for some therapeutic agent classes. The tools I developed are now being used by dozens of laboratories. All PresentER vectors are available on AddGene.

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