A clinical trial set to start this month will modify ovarian cancer cells and return them to patients to stimulate an immune response to tumors.PJD/Science

Blood-cleansing method faces its first test as cancer vaccine

New clinical trial aims to use whole, light-inactivated tumor cells for immunotherapy

Mitch Leslie

In some parts of the world, donated blood or blood components such as platelets are disinfected with ultraviolet (UV) light and riboflavin, also known as vitamin B2, before being transfused into patients. Known as the Mirasol process, the technique can neutralize an assortment of viruses, bacteria, and parasites. Now, a group of researchers wants to conscript the procedure to fight cancer, inactivating tumor cells and then reintroducing them into the body to try to set off a helpful immune response. They’ve already tested the approach in mice and dogs, and a phase 1 trial is set to start this month in patients with ovarian cancer.

“The hope would be that this will slow or prevent relapse” in combination with other therapies, says chemist Ray Goodrich of Colorado State University, who helped develop the Mirasol process more than 20 years ago and in 2018 co-founded a company, PhotonPharma, to adapt it for fighting cancer.

Cancer vaccinologist Lana Kandalaft of Ludwig Cancer Research’s Lausanne Branch says the new vaccine could work. Because it incorporates whole cancer cells, it can deliver all of a tumor’s neoantigens, novel proteins not found on healthy body cells that the immune system can recognize, she notes. As a result, it could sidestep a common challenge with other cancer vaccines—predicting which neoantigens to include for optimal immune stimulation.

But other researchers remain skeptical. Attempts to make vaccines with whole cancer cells have a long history of failure, says Lawrence Fong, an immunologist and medical oncologist at the Fred Hutchinson Cancer Center. “As a scientist, I’d say, ‘been there, done that.’”

Goodrich started working on a method for disinfecting blood as a graduate student in the late 1980s, when HIV contamination of the blood supply was a big worry. After nearly a decade, he and his colleagues settled on a solution: Mix blood with riboflavin, which latches onto DNA and RNA molecules, and then expose the liquid to UV light, which causes the riboflavin to react with and damage any genetic material from microbes. The approach leaves pathogens unable to reproduce—although it also damages platelets, red blood cells, and proteins in the plasma, meaning patients may require extra transfusions. The procedure has been approved for use in Europe, Canada, and other countries, but not in the United States, which has OK’d other technologies for disinfecting platelets and plasma.

The idea for a vaccine came when Goodrich noticed that after white blood cells went through the Mirasol process, they were “inactivated but they were intact.” He and his colleagues speculated that generating similar cellular zombies from a patient’s cancer cells and reinjecting them might ignite an immune response against a tumor. The approach would be safe, the researchers concluded, because the UV-treated cancer cells couldn’t divide and wouldn’t be able to form new tumors.

Goodrich admits that when his group first proposed the strategy, “everyone said we were crazy.” Researchers have been trying to develop vaccines that contain whole cancer cells for more than 50 years, and although some formulations made it to clinical trials, they produced a poor immune response. None of the vaccines has been approved for humans, although one is available for pets.

The harsh methods previously used to stop cancer cells from reproducing, such as radiation, also caused them to shed their neoantigens, Goodrich says. He argues that the UV-based approach should work better because it preserves these potential immune stimulants.

The new clinical trial, launching this month at City of Hope in California and sponsored by PhotonPharma, aims to recruit eight patients with relapsed ovarian cancer. They will first undergo surgery to remove their tumors. Researchers will then expose the tumor cells to riboflavin and UV light and combine them with an immune-boosting additive known as an adjuvant to produce a custom vaccine. Participants will receive three doses of the vaccine, and researchers will check for side effects and measure immune responses.

Whether the UV-based approach will provoke a stronger response than its predecessors “is an open question,” Fong says. But the animal data the researchers have presented don’t convince him it will, he says. Immunologist Olivera Finn of the University of Pittsburgh is also a doubter. Even if the vaccine activates immune cells, tumors are adept at stymying attacks, she says. “They will encounter the reality of tumor-induced suppression” of immune responses.

Still, the idea of harnessing whole cancer cells to induce antitumor immunity is enticing—and Goodrich’s team isn’t the only one pursuing it. Earlier this year, Brenus Pharma launched a phase 1 trial of its so-called ghost cells, which are derived not from the patient’s own cells, but from standard tumor cell lines. The ghost cells are unable to reproduce, and they sport characteristic tumor antigens tagged with molecules to draw the attention of immune cells. They would be available off-the-shelf, so cancer patients wouldn’t have to wait for their cells to be processed, says George Alzeeb, an oncologist at the company.

Other research teams are trying to enlist whole tumor cells, Kandalaft notes, and that leaves her optimistic about the field. This approach “is not a dead end,” she says. “Maybe now is the time” for a whole-cancer cell vaccine to succeed.

About the author

Mitch Leslie

Mitch Leslie writes about cell biology and immunology.

Source: https://www.science.org