Abstract A149: EµTel-Jak2 T-ALL mouse model is dependent upon Myb function and susceptible to immune checkpoint therapy

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic cancer, predominantly in children but patients over 50 years are also affected. While high-intensity combination chemotherapy is effective in 90% of young patients, only 30–40% of adult patients with ALL will achieve long-term remission. Furthermore, the severe side effects observed in young and old patients highlight the need for alternative therapy options. To explore the role of drivers of ALL and thus the potential for other therapy options we crossed EµTEL-JAK2 mice, a mouse model of T-ALL, with MybPlt4/Plt4 mice, which express hypomorphic alleles of Myb resulting in 40% of WT Myb function. EµTEL-JAK2 x MybPlt4/Plt4 mice showed a significant prolonged survival compared to EµTEL-JAK2 Myb+/+ mice, indicating that EµTEL-JAK2 cells are dependent upon fully functional Myb. Hence, we initiated a preclinical study targeting Myb with our TetMyb DNA vaccine combined with immune checkpoint inhibitors in C57BL/6 mice bearing transplanted Eµ TEL-JAK2 T-ALL cells. Interestingly, therapeutic treatment with TetMyb DNA vaccine and anti-PD-1 antibody therapy did not enhance overall survival. However, therapeutic monotherapy with anti-CTLA-4 antibody therapy on day 2, 7, 12, 16 and 21 after EµTEL-JAK2 transplant significantly reduced leukemic cell frequency in the peripheral blood and significantly prolonged survival. Further evaluation, especially in combination with current standard of care, is needed, but our results suggest a promising therapeutic option of anti-CTLA-4 antibody therapy in T-ALL. Citation Format: Sara Roth, Shienny Sampurno, Michaela Waibel, Leonie Cluse, Lloyd A. Pereira, Ricky W. Johnstone, Robert G. Ramsay. EµTel-Jak2 T-ALL mouse model is dependent upon Myb function and susceptible to immune checkpoint therapy [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A149.