Preclinical Characterization of Cell-Based IL12 Immunotherapy Against Murine Acute Lymphoblastic Leukemia Using Intravital Imaging

Acute lymphoblastic leukemia (ALL) is a disease of the bone marrow (BM) microenvironment, in which ALL-stroma interactions, signaling molecules, and low oxygen tension all contribute to leukemia development and maintenance. The cytokine interleukin 12 (IL12) is a key primer of the initial specific T-cell immune response for resisting cancer progression, however its potential as an anti-leukemia immunotherapeutic agent has been largely under-examined. One potential reason for this oversight is the inability of current experimental systems to recapitulate the complex BM microenvironmental system ex vivo or obtain the resolution necessary in vivo to study the precise mechanism of effect for such proposed immunotherapies. Recently, our lab has developed a novel femur window chamber (FWC) intravital imaging mouse model capable of long-term spatiotemporal assessment of leukemias within the in vivo femoral BM at cellular resolution. We used this technique to characterize a new cell-based IL12 immunotherapy, in which patients are injected with their own blast cells engineered to express IL12. This approach has shown significant potential in preliminary preclinical trials, although its mechanism of effect is still unknown. Our study sought to establish the precise interaction between the modified IL12-expressing blast cells with the BM ALL population and immune system to determine a) how long post-ALL engraftment IL12 therapy continue to be effective, b) the optimal treatment administration route, and c) whether repeated infusions will yield added benefit.