1028 – EXOGENOUS AND ENDOGENOUS IMMUNE TARGETING OF HEMATOLOGICAL MALIGNANCIES

Abstract

Chimeric antigen receptor-engineered T cells and bispecific antibodies have proven to be effective therapies for a range of leukemias, whereas modalities that rely on endogenous T cell responses including immune checkpoint blockade have not proven as beneficial. This has been attributed to a lack of elicited endogenous responses against relatively low mutation burden ALL and AML tumors, particularly in pediatrics. Here we will discuss the identification and characterization of endogenous fusion- and neoantigen-specific T cell responses in pediatric leukemias, as well as attempts to identify such responses arising during CAR T cell therapies via epitope spreading. Novel methods for efficiently detecting these responses will be described, along with the T cell features that characterize successful anti-tumor immunity.