Gabriele Casirati, M.D., Ph.D.
Dana Farber Cancer Institute, Boston, MA, USA
Finalist Essay: Stem cells in disguise: How epitope editing can empower targeted cancer immunotherapies
Abstract:
Adoptive immunotherapies have revolutionized the treatment of several tumors. Nonetheless, their application to acute myeloid leukemia is limited by the lack of actionable tumor-restricted antigens.
Precise gene-editing of surface proteins in hematopoietic stem cells may endow them with selective resistance to chimeric antigen receptor T cells or monoclonal antibodies, thus minimizing on-target/off-tumor toxicity.
We identified single amino-acid changes in the extra-cellular domain of FLT3, KIT, and CD123 that abrogate their recognition by therapeutic antibodies while preserving the proteins’ function and regulation.
These mutations can be introduced, either alone or in combination, in healthy stem cells by adenine base editing and enable the selective eradication of leukemia xenografts in murine models, while sparing human hematopoiesis. Epitope editing is a new concept in cancer immunotherapy that will provide novel opportunities to target hard-to-treat hematological malignancies.
About Gabriele Casirati
Gabriele Casirati received his MD degree from Università degli Studi di Milano and trained as a hematologist at Università Vita-Salute San Raffaele.
During 2020-2023, he worked as a research fellow at Dana Farber Cancer Institute and completed a Ph.D. in Molecular and Translational Medicine from Università Milano-Bicocca.
He is currently a postdoctoral research fellow at Boston Children's Hospital.
His research focuses on new gene-editing approaches to enhance targeted immunotherapies for hematological malignancies.