Hints That Breakthrough CAR-T Therapy May Fight Solid Tumor Cancers

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An immune system-based therapy that’s proven effective against blood cancers also might prove useful in battling solid tumor cancers, early clinical trial data show.

A small group of patients with testicular and ovarian cancer appeared to respond well to “CAR-T” treatment with immune system cells that were genetically reengineered to target their tumors, researchers said Sunday during a presentation at an American Association for Cancer Research meeting, in New Orleans.

About 86% of patients with recurring or persistent cancer had their tumor stop growing or start to shrink, and 43% had a significant decline in their tumors, said lead researcher Dr. John Haanen, a medical oncologist at the Netherlands Cancer Institute in Amsterdam.

“The nice thing also is that it is what we call an unmet need cancer patient population, because there’s hardly anything available for patients with testicular cancer who’ve failed other lines of treatment,” Haanen said. “So it’s especially nice this treatment seems to work so well.”

The experimental therapy featured an additional innovation to boot. Doctors used an mRNA vaccine — created using the same technology that developed the COVID-19 vaccines — to boost some patients’ immune response against the cancer.

“The idea was that by doing that, these cells would further expand and persist for a prolonged bit of time,” Haanen said of the mRNA vaccine.

Since 2017, six chimeric antigen receptor T-cell (CAR-T) therapies have been approved by the U.S. Food and Drug Administration, all for the treatment of blood cancers such as leukemia and lymphoma.

In this therapy, a cancer patient’s own immune cells are removed from their body and engineered to better detect their tumor cells. The trick is to find targets on the tumor cells that aren’t also found on healthy cells.

Many blood cancers share a common target unique to tumor cells, and so CAR-T therapies have mainly focused on them, said Dr. Vincent Lam, an assistant professor of oncology at Johns Hopkins University in Baltimore.

It’s also harder for CAR-T immune cells to travel to and infiltrate a solid organ tumor, compared to blood cancers, he added.

But for this trial, Haanen and his team created a CAR-T therapy that focuses on a target called CLDN6 that’s unique to some solid tumor cancers but not expressed in healthy tissue.

Prostate, ovarian and endometrial cancers, in particular, appear vulnerable to a CAR-T therapy targeting CLDN6, Haanen said. (Endometrial cancer begins in the lining of a woman’s uterus.)

Researchers tested the therapy in 16 patients, in early trials designed to check for safety and potential effectiveness.

Patients either received the CAR-T cells alone or with booster doses of CARVac, an mRNA vaccine developed by BioNTech, the company that co-founded the first COVID vaccine with Pfizer. BioNTech funded this study.

The mRNA vaccine, delivered intravenously, helped refresh the CAR-T response by prompting the spleen and lymph nodes to produce copies of CLDN6, much as the COVID vaccine produces copies of the virus’ spike protein, Haanen and Lam said.

“This is really the first clinical data that we have to show that … vaccines can potentially boost the CAR-T persistence in the patient’s body, therefore affecting a more durable response,” Lam said.

About 40% of the patients developed cytokine release syndrome, a systemic inflammation that’s common with immune-system therapies like monoclonal antibodies.

This side effect caused fever and elevated blood pressure in the patients, but was “easily manageable” with drugs that moderate immune response, Haanen said.

Both Haanen and Lam warned that these results are very early.

Safety trials are still ongoing, and the next step will be to test in patients with specific types of cancer, Haanen said.

“We really still have a long way to go to really gain sufficient confidence that this truly will work,” Lam said. “But it’s definitely a very promising signal.”

Findings presented at medical meetings are considered preliminary until published in a peer-reviewed journal.

More information

The U.S. National Cancer Institute has more on CAR-T therapy.

SOURCES: John Haanen, MD, PhD, medical oncologist, Netherlands Cancer Institute, Amsterdam; Vincent Lam, MD, assistant professor, oncology, Johns Hopkins University, Baltimore; April 10, 2022, presentation, American Association for Cancer Research, annual meeting, New Orleans

Source: HealthDay

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