CAR T cell therapy can be effective in targeting brain tumor cells, but recent City of Hope research published in Cancer Discovery
demonstrates that the treatment can also activate immune cells within a tumor microenvironment and enhance the therapy’s efficacy.
“Immune cells are present in the tumor microenvironment even as the tumor is progressing,” said Darya Alizadeh, Ph.D., the study’s lead author and an assistant research professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope. “We wanted to know if CAR T cells could reshape the tumor microenvironment to change the function of the immune cells toward targeting the tumor,” Alizadeh added.
The team’s research was also prompted by the success of a CAR T glioblastoma (GBM) patient treated in a City of Hope trial that targeted the IL13Ra2 protein.
The research team wanted to know why the patient had such a strong response against tumors.
Analyses of the patient’s samples — before and during CAR T cell therapy — revealed that the host immune cells were more reactive to the tumor following CAR T therapy.
City of Hope is a worldwide leader in CAR T therapy for GBM. It was the first institution worldwide to treat brain tumor patients with CAR T therapy, to target the IL13Ra2 protein and to deliver CAR T cells directly to the brain.
“CAR T cell therapy mediates antigen-dependent and -independent anti-tumor activity. During a productive CAR T therapy, CAR T cells can activate the host immune cells and have the potential to reshape the glioma microenvironment,” Alizadeh said.
Learnings from these findings will be important for future CAR T cell therapy designs developed by City of Hope.
The paper is titled IFNy is Critical for CAR T Cell Mediated Myeloid Activation and Induction of Endogenous Immunity
. The study was directed by senior author Christine E. Brown
, Ph.D., The Heritage Provider Network Professor in Immunotherapy. Other City of Hope authors include Robyn A. Wong, Madeleine Maker, Maryam Aftabizadeh, Xin Yang, M.D., Ph.D., Joseph R. Pecoraro, John D. Jeppson, Brenda Aguilar, Renate Starr, M.S., and Stephen J. Forman, M.D.