Development of Immunotherapy Targeting U5 snRNP200 for the Treatment of Hematologic Malignancies
Jennifer Lewis
Memorial Sloan Kettering Cancer Center
Project Term: July 1, 2023 - June 30, 2024
The therapeutic landscape of acute myeloid leukemia (AML) has witnessed considerable expansion following recent U.S. FDA endorsements of novel therapies; however, the 5-year survival rate for most adult patients remains below 10%. The absence of immunotherapeutic options for AML can be attributed, in part, to the dearth of identified antigens that selectively discriminate between AML cells and normal hematopoietic precursor cells. Through extensive investigative efforts, our laboratory has made a significant discovery of a membrane antigen, U5 snRNP200, which exhibits promising potential for Fc-engineered anti-U5 snRNP200 therapy. The overarching objective of this endeavor is to engender a novel cellular immunotherapeutic modality with the potential for broad therapeutic impact across a diverse spectrum of myeloid and lymphoid hematologic malignancies.
The therapeutic landscape of acute myeloid leukemia (AML) has witnessed considerable expansion following recent U.S. FDA endorsements of novel therapies; however, the 5-year survival rate for most adult patients remains below 10%. The absence of immunotherapeutic options for AML can be attributed, in part, to the dearth of identified antigens that selectively discriminate between AML cells and normal hematopoietic precursor cells.
Through extensive investigative efforts, our laboratory has made a significant discovery of a membrane antigen, U5 snRNP200, which exhibits promising potential for Fc-engineered anti-U5 snRNP200 therapy. U5 snRNP200 is an extensively expressed RNA helicase and a fundamental component of the spliceosome, typically sequestered within the nucleus. Nevertheless, our laboratory has validated the cell surface localization of U5 snRNP200 in AML cells. Leveraging this antigenic specificity, we are actively engrossed in the development of immunotherapy targeting the cell surface U5 snRNP200, an entity conspicuously absent from standard hematopoietic stem and progenitor cells, thereby endowing it with salient promise as an AML therapeutic candidate.
Moreover, a notable revelation from our investigation pertains to the unexpected expression of U5 snRNP200 on B cells. Consequently, we are conducting an assessment of immunotherapy efficacy on B-cell malignancies, including B-cell leukemia. The overarching objective of this endeavor is to engender a novel cellular immunotherapeutic modality with the potential for broad therapeutic impact across a diverse spectrum of myeloid and lymphoid hematologic malignancies.