City of Hope physicians have successfully treated blood cancers with chimeric antigen receptor (CAR) T cell therapy
, and they are working to expand that therapy to patients with solid tumors.
But in order to make that happen, research needs to take place in a laboratory to test the effectiveness of new CAR T therapies and also the CAR design, which consists of the different components of a CAR T cell.
CAR T cell therapy involves taking immune cells known as T cells from a patient’s bloodstream, reprogramming them in a laboratory to recognize and attack a specific protein found in cancer cells, then reintroducing them into a patient’s system, where they get to work destroying targeted tumor cells.
“Developing a CAR T cell therapy for solid tumors is particularly challenging because they need to first reach the solid tumor and then survive in a harsh microenvironment that is filled with cancer cells and other cells that make up the tumor mass,” said Saul Priceman, Ph.D.
, assistant research professor in City of Hope's Department of Hematology & Hematopoietic Cell Transplantation
Priceman and his research team compared different CAR designs that would critically impact the T cell’s ability to fight prostate cancer
that has metastasized to the bone. Their research, which used preclinical animal models, was published in a recent edition of OncoImmunology
The research ultimately identified a specific CAR design that allowed for optimal cytokine production (chemical messengers that help enhance the antitumor activity of a CAR T cell) and destruction of prostate stem cell antigen (PSCA)-positive prostate cancers by the CAR T cells.
“These CAR T cells homed to prostate cancer cells in the bone, expanded there and demonstrated robust antitumor responses,” said Priceman, the study’s lead author.
The therapy also allowed these T cells to persist for a longer period of time and kill multiple tumor cells, compared with other therapies.
“T cells, once they kill, can also die. We like to equate it to a bee sting — if a bee stings, it then dies. But a CAR T cell has to be able to kill multiple tumor cells and survive a period of time in order to control the tumor,” Priceman said.