The mRNA vaccine stimulant CAR T-therapy can help treat solid cancers

NAlthough EW ORLEANS – CAR T-therapy has been shown to cure leukemia in some people, this type of immunotherapy has so far yielded sluggish results for solid tumors such as lung or kidney cancer. But a new early-stage clinical trial presented Sunday at the American Association of Cancer Research (AACR) conference suggests that CAR D-cells can reduce some solid tumors until they are stimulated by the MRNA vaccine provided by BioNtech. .

Bioentech became a household name with the Covit-19 vaccine developed with Pfizer. Prior to the outbreak, the company was a relatively small biotechnology company focusing on developing mRNA vaccines to treat cancer. Today it is valued at $ 42 billion based on its share price, and new data show an early look at how its technology could develop new cancer treatments.

CAR T-cells use symmetric antigen receptors to detect and destroy cancer cells. These engraved receptors bind to the protein on the surface of the cancer cell. Once bound, CAR stimulates its T-cell to kill the cancer cell. In the work presented at the AACR meeting, the researchers used a target called cladin-6, which is commonly found in testicular, ovarian and endometrial cancer cells, explained John Hannen, cancer research researcher and lead author at the Netherlands Cancer Institute. Study. This helps the CAR T-cell to see and attack these cancer cells.

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BioNTech’s new treatment requires a two-step process. First, CAR T-cells are injected into a patient, which can detect and attack the cancer. After a few days, the patient is given the mRNA vaccine, which has a genetic code for claudin-6. The idea is that immune cells, called antigen-producing cells, take the vaccine, produce cladin-6, and then deliver the protein to the circulating CAR T-cells. Stimulates D-cells designed to start multiplying and producing cytotoxic compounds that can kill cancer cells.

In a press release from AACR, investigators reported that after CAR T injection, patients received occasional mRNA vaccination throughout the study.

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The idea behind the MRNA vaccine, Hanen said in his AACR presentation, was to expand the initial population of CAR D-cells and to be at a higher level and higher activity. This allows the implanted cells to get into a tumor and stay there to kill the cancer cells. Based on the initial results, Hanen said it seems to have happened. Of the 16 patients treated in the study, 14 were evaluated for effectiveness, of which, six found their tumors to shrink or disappear, Hanen said.

“I was very skeptical at first because CAR D-therapy had not worked on solid tumors before, so we were very excited to see how the metastases disappeared and the patients improved,” Hanen said. “These patients had an amazing partial response, and one patient had complete relief. It is still ongoing and has been going on for almost six months now.”

This is preliminary work, but promising, said Henry Fung, head of bone marrow transplantation and cellular therapies at the Fox Chase Cancer Center in Philadelphia, who was not involved in the investigation. “CAR D-cell therapy has become the standard of care for selected patients [blood cancers,]Fung said in a statement sent an email to STAT. “Previous studies for solid tumors have been disappointing. Here, a CAR T-cell product targeting cladin-6 is innovative and shows promising results in selected solid tumors – the impact of the effects is not clear.

The use of the mRNA vaccine to increase a patient’s CAR T-cell population is an idea that could make future work better in cell therapy, said Christine Anderson, a cell therapy researcher at the Fred Hutchinson Cancer Research Institute who did not work on the experiment. STAT. “Part of the problem with cell therapy in solid tumors is that you do this work to engineering the D cells, which then do not penetrate the tumor, but if they do, they will not last long,” he said. It’s exciting to see that. “

But Anderson added that there are unanswered questions in this research. For one, the results are too quick to accurately assess the clinical efficacy of this approach, he said. The greater the number of participants in the more in-depth Phase 2 experiment the longer it will have to follow. Although the researchers did not find severe toxicity in this initial test, it is possible that larger and longer studies may reveal more toxic side effects, especially since patients with this stage 1 test showed mild signs of pancreatic toxicity. In rare cases, claudin-6 has been found in healthy adult tissues, including the pancreas.

When asked about off-tumor toxicity to Hannon at the AACR, he acknowledged that it was possible. “We don’t know what will happen if we treat patients too much,” he said. “This is something we still have to learn.”

Many patients may need additional power-ups for cell therapy in addition to an MRNA vaccine stimulus to completely eradicate the cancer, Anderson added. “I don’t know if just increasing it will be enough. Late onset disease does not involve the removal of tumors from multiple mouse models, ”he said, adding that many patients will have to attack solid tumors harder by combining cell therapy with other immunosuppressive drugs to generate deeper responses.

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