Immune Monitoring Core

PROJECT SUMMARY/ABSTRACT Immunotherapy has advanced tremendously in the past decade and cellular products are now being leveraged efficiently in a number of settings. Third party targeted therapeutic Immune Effector Cell (IEC) interventions are bound to change the way we treat AML and ALL. NK cell products hold promise because of their ability to quickly kill tumor cells without causing graft versus host disease (GVHD). Similarly, tolerance inducing regulatory T cells (Tregs) are a T cell population with cytolytic as well as tolerance induction potential. Furthermore, in the allogeneic setting, Tregs suppress GVHD and graft rejection. This grant focuses on clinical implementation of novel Treg and NK targeted therapeutics in AML and ALL, as well as development of novel CAR-iTregs and CAR-iNKs. An overarching hypothesis of this PPG is that allogeneic Treg and NK cell immunotherapies can be engineered to maximize successful leukemia control with decreased toxicity, when compared to conventional T cell immunotherapy approaches. To that end, Core C will provide seamless sample processing and state-of-the- art assays to best inform the projects on how IEC cell interventions work in the clinic and help assess how novel IEC products perform pre-clinically. The Core integrates the processing, storage/annotation, distribution, and analytic capabilities of the Translational Therapy Laboratory, an NCI funded Cancer Center Support Grant shared resource, with a number of novel techniques to gain deep understanding of Treg and NK cell biology, the immune landscape influencing and resulting from IEC intervention, and the tumor microenvironment (TME) the IEC cell interventions must operate in. Mass cytometry, CyTOF, will be used to phenotypically evaluate IEC products and immune reconstitution at a high level of detail. CyTOF analysis of bone marrow samples will also be leveraged to evaluate the TME. Cytolytic assays will be used to determine IEC function pre-clinically and after patient treatment. Assays will be carried out equally across all projects to determine differences in pharmacokinetic and pharmacodynamic profiles of each of the products so they can be fairly compared to each other and inform project leaders on how to best implement IEC interventions. Uniform, high-quality data generated in these studies will be integrated with clinical outcomes, in collaboration with Cores A and B, and will be made available to all of the projects in order to maximize synergy and limit variation generated by having different laboratories carry out assays for individual projects.