So far, the wonders of chimeric antigen receptor (CAR) T-cell therapy have only been seen in blood cancers. Investigators at Moffitt Cancer Center report findings that show a potential target in solid tumors.
Investigators from Moffitt Cancer Center in Tampa, Florida, have published results identifying a potential target for chimeric antigen receptor (CAR) T-cell therapies in solid tumors—which could be step toward bringing this game-changing treatment beyond blood cancers.
In Molecular Cancer Therapeutics, a publication of the American Association of Cancer Research, the Moffitt team present the identification of OR2H1, an olfactory receptor that they demonstrate inhibits growth in lung and ovarian tumors.
The creation of individualized CAR T-cell therapy involves genetic modification of a patient’s own T cells, which are collected through apheresis and then put through a manufacturing process; the cells are modified to include a gene for the T cell receptor that allow them to hunt down the cancer in the body when the treatment is infused back into the patient.
Finding tumor markers that will make this process work in solid tumors has been a huge challenge. The Moffitt team, led by Jose Conejo-Garcia, MD, PhD, has zoned in on proteins—the olfactory receptors—that are expressed in the nose but are also found in many solid tumors, and very few normal cells.
The investigators created CAR T cells specific to the OR2H1 protein, which were able to kill lung and ovarian cells that expressed OR2H1—but did nothing to healthy cells. The same effect was seen in mice implanted with human tumors with varying levels of OR2H1.
“Our work demonstrates the applicability of this therapy to a wide variety of patients, given the expression of OR2H1 in a subset of solid tumors across multiple histologies, including high-grade serous ovarian cancers, lung carcinoma, cholangiocarcinoma, prostate cancer and ovarian cancers of multiple other histologies,” Conejo-Garcia, chair of Moffitt’s Department of Immunology, said in a statement. “Targeting a molecule that is not expressed in vital tissues would allow us to further engineer T cells to overcome immunosuppression at tumor beds, if needed.”
Martin AL, Anadon CM, Biswas S, et al. Olfactory receptor OR2H1 is an effective target for CAR T cells in human epithelial tumors. Mol Cancer Ther. Published online May 2, 2022. https://doi.org/10.1158/1535-7163.MCT-21-0872