Reprogramming T cells on the fly to fight cancer

Dr. Matthias Stephan

CANCER DIGEST – May 10, 2017 – The idea of using the body’s own immune system to halt cancer has a long history of research approaches. One of the most promising in that vein over the last decade has been immunotherapy, and most recently the use of T cells engineered with chimeric antigen receptors or CAR T cells.
These T cells are extracted from a patient, engineered in the laboratory to specifically recognize the genetics of the patient’s tumors, and then grown into large volumes and transfused back into the patient. The process takes several weeks and can’t be generalized to all patients with that cancer type, it is an individual treatment.

But what if you could engineer the cells inside the body and allow them to grow and multiply until they mount an effective attack that can eradicate the cancer? That’s the approach Dr. Matthias Stephan and colleagues at Fred Hutchinson Cancer Research Center in Seattle are taking. They are using nanotechnology to carry the tumor-targeting genes directly to the T cells to reprogram them to attack the cancer.

In a proof-of-principle study, Stephan’s team showed that nanoparticle-programmed T cells significantly slowed the progression of leukemia in a preclinical model. The process uses nanoparticles, sub molecular "trucks" programmed to stick to T cells where they then deliver CAR-encoding genes into the T cells, thus reprogramming the T cells to recognize the patient’s cancer.

In the study they compared the CAR-carrying T cells in a laboratory model of the cancer and found that the nanoparticle CAR T cells performed similarly to conventional CAR T cells grown in the lab and reinfused into the patient.

Stephan’s nanoparticles still have to clear several hurdles before they are cleared for human trials. He’s pursuing new strategies to make the gene-delivery and -expression system safe in people and working with companies that have the capacity to produce nanoparticles at clinical grade.