Stephen P. Schoenberger "Towards personalized immunotherapy of solid tumors" - 19 dicembre ore 17.00

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Prof. Stephen P. Schoenberger, Ph.D, Professor, La Jolla Institute for Allergy and Immunology, Translational Science Director, Center for Personalized Cancer Immunotherapy, UCSD Moores Cancer Center, USA

 

"Towards personalized immunotherapy of solid tumors"

 

Tumor-specific neoantigens represent an attractive class of targets for the personalized immunotherapy of cancer due to their unique expression within neoaplastic cells. Although expressed somatic mutations can be readily identified through next-generation DNA/RNA sequencing and bioinformatics analysis, their validation as neoantigens generally requires in-silico epitope prediction algorithms to reduce the number of candidate peptides which can be tested for T cell response from a given patient’s lymphocytes, with most approaches being focused on one type of T cell (CD8+) producing a single type cytokine (IFN-g). We sought to evaluate whether an unbiased approach would allow a broader and more accurate picture of neoantigen-specific T cell responses to be visualized in HNSCC, a tumor type in which the modest mutational load allows all mutated peptides to be tested by 2-color ELISPOT analysis for both CD4+ and CD8+ T cells capable of producing IFN-g or IL-5.  Our results indicate that pre-existing T cell responses against both driver and ‘passenger’ mutations are relatively common and that both type 1 (IFN-g) and type 2 (IL-5) cytokine responses can be detected from restimulated PBL. To facilitate preclinical modeling of adoptive cell therapy (ACT) of HNSCC, we have additionally developed a patient-derived xenograft platform that features conditionally reprogrammed cell lines that preserve expression of neoantigens detected in the primary tumor and which are recognized by neoantigen-specific autologous T cells. The application of these findings and platform for the development of personalized immunotherapy will be discussed.


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