Potential Cancer ‘Vaccine’ Shows Promise in Early Non-Hodgkins Trial

Researchers with the Icahn School of Medicine at Mount Sinai in New York have had promising results with a cancer vaccine in an early-stage clinical trial. They published their work in the journal Nature Medicine.

Indolent non-Hodgkin’s lymphomas (iNHLs) do not respond to standard cancer therapy and respond poorly to checkpoint inhibitors. The research group, led by Joshua Brody, Director of the Lymphoma Immunotherapy Program at Icahn, showed that lymphoma cells could directly prime T-cells, but that actual immunity required multiple exposures, or cross-presentation.

Brody and his team developed a therapy that combined Flt3L, radiotherapy, and a TLR3 agonist, “which recruited, antigen-loaded and activated intratumoral, cross-presenting dendritic cells (DCs),” the authors wrote.

Brody told Live Science, “We’re seeing tumors all throughout the body melting away,” after injecting a single tumor.

The vaccine was tested in 11 patients with NHL. Not all patients responded to the therapy. But some of the patients, three, went into remission for relatively long periods. Because of its promise, the vaccine is now being tested in breast and head-and-neck cancers. The vaccine also appears to increase the effectiveness of checkpoint inhibitors in the disease, what Brody told Live Science “are remarkably synergistic.”

The treatment isn’t exactly a vaccine. That’s a word used for anything that provides long-lasting immunity against disease. But this new treatment, which is a type of immunotherapy, does involve injecting patients with two types of products that stimulate the immune system.

The therapy is a three-step process. First, patients receive an injection into the tumor of a compound that recruits dendritic cells, a type of immune cells. Dendritic cells send messages to T-cells, another type of immune cells, to attack the tumor. Then the patients receive a low dose of radiotherapy, which kills some of the cancer cells so they release antigens that the immune system can recognize. The dendritic cells identify those antigens and alert the T-cells.

Patients are then given a second injection of a compound that activates the dendritic cells. “The dendritic cells are learning the lesson … and telling it to the T-cells,” Brody told Live Science.

In mice, the researchers found that using a checkpoint inhibitor with their “vaccine,” about 75% went into long-term remission.

Brody told CNBC, the treatment “has broad implications for multiple types of cancer. This method could also increase the success of other immunotherapies such as checkpoint blockade.”

Silvia Formenti, Chairwoman of Radiation Oncology at Weill Cornell Medicine and New York-Presbyterian, who was not involved in the study, told CNBC, “It’s really promising, and the fact you get not only responses in treated areas, but areas outside the field [of treatment with radiation] is really significant.”

But the research is very early and conducted in a small group of patients. Eric Jacobsen, Clinical Director of the Dana-Farber Cancer Institute’s lymphoma program, told CNBC, “It’s definitely proof of concept, but larger studies are definitely needed and additional strategies to try to get more than three out of 11 patients to respond.”

The research was funded by The Damon Runyon Cancer Research Foundation, the Cancer Research Institute and Merck. Celldex and Oncovir provided the laboratory work and materials for the trial.

https://www.biospace.com/article/cancer-vaccine-shows-promise-in-early-trial/