Challice Bonifant, MD, PhD
Assistant Professor, Department of Pediatrics and Communicable Diseases
Division of Hematology/Oncology
Challice Bonifant, MD, PhD is an assistant professor of Pediatrics and Communicable Diseases in the Division of Hematology/Oncology.
AML is a cancer with a poor prognosis, particularly for high-risk, relapsed, and refractory disease. Cell therapy has been successful in the treatment of hematological malignancies, but is limited in that anti-tumor effect is dependent on expansion and persistence of AML-specific effector cells. To overcome this limitation, we use retroviral delivery of coding sequences ex vivo in order to generate T cells that express chimeric antigen receptors targeting an AML-specific antigen. These cells are specifically activated by target antigen, and exhibit specific anti-AML cytotoxicity. We are investigating the biological impact of incorporating distinct co-stimulatory domains within our chimeric proteins to optimize AML killing and T cell persistence. We have also employed cellular engineering in order to produce cells that constitutively secrete bispecific engager molecules that recognize AML and are agonistic at CD3ε of the T-cell receptor complex. Once activated by the engager molecule, T cells in the environment are directed to kill leukemia cells. We are additionally engineering primary NK cells to enhance our understanding of NK cell immunobiology. While primarily focused on enhancing the anti-AML immune response, we are also studying AML-specific immune evasion, to determine the contribution of checkpoint ligation to engineered T cell immunosuppression.