Evaluating the Potential of Harnessing Anti-Leukemia T cells for Treating T-ALL

• Published in: The Journal of immunology (1950) 2021-05, Vol.206 (1_Supplement), p.67-67.23
• Main Authors: Triplett, Todd A, Rios, Joshua, Kottapalli, Srividya, Weinberg, Andrew D, Somma, Alexander, Sandoval, Trevor
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.206.Supp.67.23

T cell Acute Lymphoblastic Leukemia (T-ALL) is a devastating malignancy found primarily in pediatric populations. Although patient outcome has improved, standard of care for T-ALL has not progressed from intensive regimens of chemotherapy. Immunotherapy may offer an alternative approach for treating T-ALL with lower toxicity profiles. In the case of B-ALL, adoptive transfer of engineered cells (e.g. CAR cells) has had resounding success. Unfortunately this may not translate to T-ALL due to severe immunodeficiency from ablating the T cell compartment. These studies therefore sought to determine the therapeutic potential of harnessing anti-leukemia T cells that spontaneously arise in tumor-bearing hosts in response to T-ALL. As very little is known about the interplay between T-ALL and T cells, we initially examined changes to the T cell compartment in response to T-ALL during disease progression by transplanting primary leukemia cells into immune-competent, congenic mice. This model revealed an increase in effector memory CD8 T cells with increased levels of PD1 and OX40 that largely correlated with tumor burden. Importantly, co-targeting PD1 with OX40 resulted in drastic reduction in tumor burden while expanding actively proliferating CD8+GrzB+ T cells. To gain a better understanding of T cell interactions with T-ALL in situ, we have begun utilizing NanoString Technologies’ Digital Spatial Profiling platform. This platform has already shown distinct functional states of T cells between those interacting with leukemia compared with those at distal sights. Ongoing studies aim to identify therapeutic targets in multiple organs which can activate T cell populations of interest to maximize their anti-leukemia effector responses.