# Enhancing Chimeric Antigen Receptor T Cell Therapies for HematologicMalignancies: Beyond CART 19 > **NIH NIH P01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $3,119,164 ## Abstract OVERALL PROJECT SUMMARY / ABSTRACT The long-term goals of this renewal P01 are to develop next generation immunotherapy with chimeric antigen receptor (CAR) T cells and to translate this research into new therapies with curative potential for patients with blood cancer. The CAR developed at our center was the first cell and gene therapy to ever receive approval from the FDA, initially for refractory/relapsed pre-B cell acute lymphocytic leukemia (ALL) in 2017 and lymphoma in 2018. However, multiple myeloma (MM), acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) remain as the major unmet medical need in blood cancers. Our central hypothesis is that therapies with combination of CAR T cells and advanced forms of human genome editing will enable this powerful therapy to reach a broader spectrum of patients with blood cancer. We have brought together a cadre of exceptional investigators from multiple disciplines who have collaborated and published together for many years. Each disease-focused project will be led by recognized authorities in the field. To achieve our goals, we have three Projects that build on progress during the previous funding period and will continue to coordinate closely with essential shared resource cores. In Project 1, we will determine the clinical and immunological impact of treating patients on two clinical trials: (i) CAR T cells targeting CD19 will be tested with genetic disruption of CD5, CTLA- 4 and TET2 to address CLL and lymphoma, which is lack of sustained effector CAR T function in these patients. In AML, the central problem in CAR T cell therapy is the lack of a known surface antigen that is present on AML but lacking from normal hematopoiesis. The goal of Project 2 is to open a wide therapeutic window for AML by genetically-modifying normal marrow to make it resistant to killing by anti-AML CAR T cells, and delivering potent anti-leukemic CAR T cells specific for CD45. Engineered HSC that are genetically edited to install a hematopoietic system facilitating non-toxic therapy with these potent CAR T cells will be developed. In Project 3, the overall hypothesis is that anti-myeloma efficacy will be maximized by (i) testing the efficacy of marrow- derived CAR T compared to current standard of care blood-derived CAR T (ii) improving persistence of BCMA CAR T with orthogonally mutated IL-2/IL-2R technology and mRNA/lipid-nanoparticle vaccine technology to overcome suboptimal persistence and efficacy of current BCMA T cells. The Scientific and Administrative Cores for this P01 are essential for our progress including provision of project management for collaboration and biostatistics, clinical safety and monitoring, and fiscal support (Core A), a GMP facility for manufacture of cells and identification of new binders for CAR targets (Core B), and a state-of- the-art platform for GLP analysis to provide high dimensional data of the samples generated in all Projects (Core C). Our renewal application has ... ## Key facts - **NIH application ID:** 10931406 - **Project number:** 5P01CA214278-07 - **Recipient organization:** UNIVERSITY OF PENNSYLVANIA - **Principal Investigator:** CARL H. JUNE - **Activity code:** P01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2024 - **Award amount:** $3,119,164 - **Award type:** 5 - **Project period:** 2017-08-15 → 2028-08-31 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/10931406 ## Citation > US National Institutes of Health, RePORTER application 10931406, Enhancing Chimeric Antigen Receptor T Cell Therapies for HematologicMalignancies: Beyond CART 19 (5P01CA214278-07). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10931406. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*