Increasing access to CAR T-cell cancer gene therapy

Cancer researcher Shikhar Mehrotra, Ph.D., in his lab

by Ryn Thorn

Cancer is universally daunting and scary. However, not all cancer treatments are universally accessible.

Associate Scientific Director at MUSC's Center for Cellular Therapy, Shikhar Mehrotra, Ph.D., aims to make a specific type of gene therapy called chimeric antigen receptor (CAR) T-cell therapy more accessible.

CAR T-cell therapy trains a patient’s own immune cells to attack cancerous tumors.

"There are certain antigens on tumors that can be identified by T-cells, and these T-cells can kill the tumor," Mehrotra said. "The whole idea is that you can give normal T-cells in the human body eyes so that they can see the tumor antigen."

In CAR T-cell therapy, white blood cells are taken from patients. Treatment facilitators either find the cells that can attack tumors or engineer them to recognize the tumors before expanding them for about two weeks. The patient then receives an infusion of their own cells modified to recognize and attack cancerous tumors with increased efficacy.

Mehrotra explained that improvements can be seen as early as about a month after a patient has received CAR T-cell therapy.

Though this therapy is only used in a small number of cancers, there are some possible side effects, and outcomes vary by cancer type, it is effective in many cases.

In their 2023 paper in the journal Nature, National Cancer Institute researchers Kathryn Cappell, M.D., Ph.D., and James Kochenderfer, M.D., described the rates of complete response—the absence of detectable cancer cells—as "outstanding."

Despite this promise, there is still a massive barrier to CAR T-cell therapy for patients: cost. One round of therapy costs around $400,000.

Life-saving access

To tackle this obstacle, Mehrotra explained that at MUSC’s Hollings Cancer Center doses of CAR T-cell therapy can be manufactured for around 1/5th of the typical cost, possibly even lower.

Despite typically only needing one round of the therapy, the $400,000 price tag puts CAR T-cell therapy off limits for most patients.

With institutional support from MUSC and philanthropic support from LOWVELO, a Hollings Cancer Center-based charity bike ride, Mehrotra and his team have laid the groundwork for this much more affordable CAR T-cell therapy for 10 patients. Mehrotra and his clinical partner, Brian Hess, M.D., recently received a fundable score on a collaborative NIH/NCI RO1 grant that will allow for 30 additional patients in this trial.

Mehrotra plans to use the momentum of treating these 40 collective patients to draw more attention to CAR T-cell therapy. Bringing in philanthropic dollars is essential, he explained, to help bring the cost of a life-saving therapy from $400,000 to around $50,000.

His next step is to go statewide. "Our homegrown product can be more available throughout the state," he said. "We are the only facility in this state that can do it."

Mehrotra and his team are also strategizing ways to use the principles of CAR T-cell therapy for a more expansive list of cancers as well: everything from skin cancer to prostate cancer. The goal is to bring this cutting-edge technology to those who need it.

Using the Center of Cellular Therapy (CCT), where the human-grade products are prepared at MUSC, Mehrotra's team is also focused on generating the data for using tumor-infiltrating lymphocytes (TILs) to propose Phase I clinical trials for treating patients with melanoma, breast, prostate, bladder, and oral cancer. This effort has been supported recently by funds from the NIH/NCI under SBIR/STTR R41 and R42 grants to Mehrotra through his spin-off biotech company, Lipo-Immuno Tech, LLC.

"Our strategy is to see how much we can broadly affect the impact of tumor-specific T-cell therapy once we get started," he explained. Ultimately, Mehrotra and his team are not only researching but also marketing their results, intending to improve cancer treatment strategies at MUSC.