Research Finds CAR T-Cell Therapy May Eliminate Tumor Cells Left After Surgery

A recent preclinical study has found that chimeric antigen receptor (CAR) T-cell therapy, an approach that reprograms patients’ own immune cells to attack blood cancers, may enhance the efficacy of surgery for solid tumors.

Surgical approaches can be curative when a solid tumor cancer has not spread. However, the space where a tumor ends and healthy tissue begins is often difficult for surgeons to discern, leading to frequent post-surgical recurrence due to remaining microscopic tumor cells. One potential approach to this problem is to apply an anti-tumor treatment to the remaining tissue margins immediately following tumor removal, thereby killing any residual tumor cells.

According to the findings, published in Science Advances, the researchers applied a special gel containing human CAR T cells to surgical wounds in mice following partial tumor removal. In almost all cases, they found that the CAR T cells apparently eliminated the residual tumor cells, allowing the mice to survive when they otherwise would have succumbed to tumor recurrence.

“As we continue to advance CAR T-cell therapy forward, finding applications for use in solid tumors is a major goal,” said senior author Carl June, MD, director of the Center for Cellular Immunotherapies at Penn Medicine’s Abramson Cancer Center, in a press release. “Based on the promising results in this study, our colleagues have planned a clinical trial in patients with locally advanced breast cancer.”

CAR T cells are engineered to target specific proteins. All approved CAR T treatments target proteins found on cancer cells and are typically harvested from the patient’s blood, engineered in a lab, and then reintroduced to the patient to work as a “living drug.”

June and his colleagues helped develop and test the first FDA-approved CAR T treatment, approved in 2017, and there are now 6 approved CAR T-cell therapies targeting a variety of blood cancers.

Despite this progress, solid tumors have been a more challenging target for CAR T treatments, partially due to tumor bulk and anti-immune defenses. However, using a mouse model of brain cancer, other researchers have found that CAR T cells may be useful for the more limited task of clearing residual cancer cells after surgery.

In the current study, June and colleagues used this same approach against 2 other cancer types: triple-negative breast cancer, which lacks all 3 major breast cancer markers, and human pancreatic ductal carcinoma, which is the most common type of pancreatic cancer. Both of these solid tumor types are notoriously difficult to cure.

The CAR T cells in the study were engineered to home in on the protein mesothelin, a surface marker on both types of tumor cells. Without the CAR T cell and fibrin gel, the remaining tumor tissue grew, and the mice succumbed within about 7 weeks. With the gel, however, residual tumor tissue quickly disappeared in 19 of 20 mice, and these mice survived without wound-healing complications or other apparent adverse effects for the remainder of the observation period.

Further experiments showed that CAR T cells targeting mesothelin have the potential to attack healthy cells bearing that protein marker after intravenous injection, and the toxicity was decreased by local injection of the CAR T cells compared to direct injection of the cells into the blood.

“This study demonstrates the promise of CAR T as an add-on to surgery for solid tumors,” June said in the press release. “We also think that this approach could be broadened to deliver other cellular therapies and anticancer agents in addition to CAR T cells, potentially boosting the antitumor effectiveness even further.”

REFERENCE

CAR T Cell Therapy May Eliminate Tumor Cells Missed by Surgery. News release. Penn Medicine News; January 11, 2023. Accessed January 17, 2023. https://www.pennmedicine.org/news/news-releases/2023/january/car-t-cell-therapy-may-eliminate-tumor-cells-missed-by-surgery