Dr. Stanley Riddell, an oncologist and immunotherapy researcher at the Fred Hutchinson Cancer Research Center in Seattle, recently presented “dramatic” results from his adoptive T-cell strategy to fight cancer at the annual meeting of the American Association for the Advancement of Science in Washington, D.C.
T cells are white blood cells that detect foreign and malignant cells, and can launch a cascade of events that attack and clear cancer cells. However, the immune response is often not potent or persistent enough to successfully eradicate tumors, and the T cells eventually become exhausted. Cancer cells are also known to develop several strategies to evade the host’s immune system and continue to proliferate, allowing tumors to spread throughout the body.
Adoptive T-cell transfer is an immunotherapy strategy in which T cells extracted from a patient and are engineered to recognize and destroy cancer cells. After T-cell extraction from the blood, researchers genetically introduce potent receptors into the cells to target cancer cells. The T cells are then re-introduced into patient’s circulation system and, ideally, travel to the tumor site and kill malignant cells.
Dr. Riddell and colleagues have developed an experimental immunotherapy in which T cells are engineered with chimeric antigen receptors (CARs), synthetic receptors that are delivered and linked to specialized subsets of T cells by gene transfer. These T cells are then redirected to recognize cancer cells, resulting in a specific and long-lasting immune response. In preliminary results of clinical trials, the researchers have observed that this immunotherapy led to sustained regression in many B-cell cancer cases — namely, acute lymphoblastic leukemia, non-Hodgkin lymphoma, and chronic lymphocytic leukemia — in patients previously described as “relapsing” or “treatment resistant.” Dr. Riddell’s research team has recently revised the CAR T-cell protocol to increase effectiveness and reduce side effects, which may include neurological symptoms and “cytokine release syndrome,” with fevers and low blood pressure.
“The merging of gene therapy, synthetic biology and cell biology is providing new treatment options for patients with refractory malignancies and represents a novel class of therapeutics with the potential to transform cancer care,” Dr. Riddell said in a press release. “In the laboratory and in clinical trials, we are seeing dramatic responses in patients with tumors that are resistant to conventional high-dose chemotherapy.”
Currently, the researchers are working on a new generation of T cells that aims to be safer, easier to design, and with application in a broader range of cancer types.