Engineering Next-Generation CAR T Cells to Treat Pediatric AML: Enhancing Safety Through Dynamic Control and Specificity
Abstract
This proposal will address at least two focus areas specified in the application guidelines: Immunotherapy and Cancer in Children, Adolescents, and Young Adults. Acute myeloid leukemia (AML) in children, adolescents and young adults is only curable in 50% of patients. Immunotherapeutic approaches are changing the landscape of treatments for patients with B-lineage malignancies but have not yet been effective in myeloid malignancies due to concerns over on-target/off-tumor effects on healthy myeloid cells leading to life-threatening myelosuppression. No AML-specific cell surface antigens have been identified. However, there are abnormal cell surface immunophenotypes that are specific to AML cells. There has not been a successful immunotherapy approach targeting the abnormal cell surface phenotypes that differentiate AML from normal myeloid cells. In the Lim lab, we have developed two novel receptors that we believe have the potential to overcome the obstacles of on-target/off-tumor toxicity. Objective/Hypothesis: Our goal is to improve the treatment of pediatric acute myeloid leukemia (AML) by developing next generation immunotherapy with enhanced AML specificity and decreased toxicity. This is a collaborative venture between a leader in T cell therapy engineering (Lim) and a leader in childhood cancers (Loh). Specifically, we will be taking two approaches using recently developed, novel receptors to generate a chimeric antigen receptor (CAR) T cell with titratable cytotoxic activity and an AND-gate, combinatorial antigen receptor CAR T cell. Using these approaches, we believe that we will be able to 1) titrate myelosuppression and 2) develop T cell circuitry to target abnormal combinations of cell surface antigens that are specific to leukemic cells and will spare toxicity to healthy myeloid cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2022
- Accession Number
- AD1170615
Entities
People
- Wendell Lim
Organizations
- University of California Regents