Engineering Inflammation-free CAR Therapy

Understanding how proteins impact inflammation associated with CAR-T cell therapies

Full Project Name:Engineering Inflammation-free CAR TherapyPrincipal Investigator:Subramaniam Malarkannan, PhD, MedicineCo-Investigator:Matthew J. Riese, MD, PhD, Medicine; Nirav Shah, MD, MedicineAward Amount:$200,000

Award Date

January2018

Project Duration:24 months

Project Description Narrative:

Treatment of refractory B cell malignancies, including B cell acute lymphoblastic leukemia (ALL), has been revolutionized with the development of therapies that make use of engineered T cells. However, inflammation is a major limitation in the use of CAR-T cells to treat cancers of B cell origin, in some instances resulting in organ malfunction and death. And inflammation associated with cytokine-release syndrome (CRS) caused by Chimeric Antigen Receptor transduced NK or T cell is a major limiting factor in the successful utilization of cellular immunotherapy for cancer.

Through this award, researchers will study unique signaling proteins that are exclusively responsible for regulating inflammation to support improved therapies for containing inflammation in cancer and other deleterious diseases such as autoimmune disorders.

Outcomes & Lessons Learned:

Established that adhesion and degranulation-promoting adapter protein (ADAP) is a molecular target to reduce inflammatory cytokine and chemokine production following CAR therapy
Initiated partnerships with two biotechnology companies during the project and will continue working with them to advance the research to the next phase
Generated data to be used for an R01 grant submission and a manuscript to further the research and share the findings
Information learned in the first year of the project was shared via a poster presentation at one international conference
Submitted two grants to advance the research
Submitted 15 publications to molecular biology, immunology, and cancer focused journals, 10 of which were published