Cell & Gene Therapy
CAR-T Cell Therapy for Solid Cancers: What's Hot in 2022
We are overcoming barriers to making autologous and allogeneic cell therapies for solid cancers
CAR-T cells are immune cells that have a chimeric, genetically modified receptor on the cell surface instead of a T cell receptor, which is not subject to normal immune cell restrictions. Most CAR-T cells are currently designed for the treatment of hematologic malignancies, leading to the recent approval of five CAR-T cell products by the US Food and Drug Administration all targeting different liquid cancer types. In the meantime, the development of CAR-T cells against targets in solid tumors is advancing to early clinical stages: allogeneic as well as autologous CAR-T cells against HER2, EGFR or PSA are currently being tested preclinically and in clinical Phase I studies. The major challenge as compared to hematological malignancies is the differences in tumor biology: as the effector and target cells are separated the critical steps the effector cells take in finding, entering, and surviving in the tumor tissue are encountering many physiological barriers.
Recent developments are helping to overcome those hurdles, however. As most of the targets for solid cancer are as well expressed in normal tissue it is crucial to either choose a target with an at least a tenfold higher expression level in tumor tissue as compared to normal tissue or to integrate a stop signal into the cell design to be able to eliminate the engineered cells when they eradicate the tumor. The expression of specific enzymes like heparanase by the CAR-T cells helped to increase the infiltration/entrance of the CAR´s into the tumor tissue. And last but not least the survival of the CAR-T cells in the tumor microenvironment can be improved by the expression of different factors reducing the oxidative stress in the hypoxic tissue. With those more sophisticated cell therapy approaches the advent of autologous as well as off-the-shelf allogeneic cell therapies for solid cancer holds promise for greater success in treating solid cancer in the near future.
-- Julia Schueler DVM, PhD, Research Director, Discovery Oncology, Charles River
Our What's Hot series are annual forecasts provided by Charles River's thought leaders. Check out here what our scientists are predicting for 2022 and what they called out in years past.