Immunotherapy Combination Aims To Improve Success of Cancer Treatment

According to a new study by immunologists at the University of Konstanz, a new cancer vaccine could enhance the positive effects of existing immunotherapy drugs and increase the success rate of treatments from 20% to 75%. The vaccine, which contains a new immune stimulant that is also suitable for use in humans, was able to partially rid the mice treated in the study of tumors. The study also showed that combining the vaccine with an immune checkpoint inhibitor - an established immunotherapy drug with a success rate of up to 20% in humans - can significantly increase the proportion of mice that respond to treatment, so that the tumor disappears in 75% of the cases. The results suggest that this new approach, where a vaccine is used in combination with established drugs, could be an effective cancer immunotherapy that should be tested in future clinical trials. The results were published in Nature Communications on May 18, 2021.

Cancer therapy has made a major breakthrough in recent years through a certain type of immunotherapy known as “immune checkpoint inhibition”. Immune checkpoint inhibitors work by stopping the body's natural immune response from shutting down and instead causing the body to continue attacking the tumor cells. This has been shown to be effective in certain types of cancer, such as melanoma and squamous cell carcinoma of the skin, lung cancer, kidney cancer, and liver cancer.

But not all cancer patients respond to this immunotherapy. For example, only 20% of melanoma patients can be cured. The reason why many of them do not respond well to treatment can be explained by the fact that the body itself has to initiate an immune response, which the drugs then prolong. If the body does not recognize its tumor cells as foreign, the immune checkpoint inhibitors have no immune cells as a starting point.

Now the team of immunologist Prof. Dr. Marcus Groettrup at the University of Konstanz developed a technique that triggers such an immune response against the tumor. The microparticle-based cancer vaccine, which uses the human-approved immune stimulant riboxxim, can evoke the body's T-cell response, which is necessary for immune checkpoint blockade drugs to be effective.

“A major shortcoming of cancer vaccines is the availability of immune stimulants that can be used in humans,” says Marcus Groettrup, senior author of the study. "In combination with the immune checkpoint blockade, our clinically applicable vaccine leads to an increase in the proportion of mice that can be cured of existing tumors to 75 percent."

A cancer vaccine safe for humans

The aim of the study was to develop a particle-based cancer vaccine that elicits an effective immune response against tumors and that is suitable for clinical use.

The team created particles 1 micrometer (or 0.001 mm) in size that contained a tumor protein and riboxxime - a molecule that stimulates the immune system to respond. Riboxxim is manufactured by Riboxx Pharmaceuticals in Dresden.

Mice injected with a single dose of the microparticle-based vaccine produced a strong anti-tumor immune response that was still detectable after eight weeks. Even very small doses of the vaccine could trigger a strong immune response compared to other immunostimulants.

The team tested the vaccine on a number of cancer protein fragments, including those from prostate cancer, breast cancer and melanoma. A strong cellular immune response was obtained against all of these antigen fragments in mice, suggesting that the new approach could be applied to a wide variety of cancers.

A synergistic combination

However, due to the natural down-regulation of the body's immune response, the tumors gradually returned 30 days after vaccination. However, if the vaccine was combined with an immune checkpoint inhibitor, the positive effects continued and the tumors were defeated.

“We were able to develop a clinically applicable cancer immunotherapy that works complementary to current immunotherapy,” says Dennis Horvath, who, together with Julia Körner, is the first author of the study. Horvath is a doctoral candidate at the Center for the Advanced Study of Collective Behavior (CASCB) at the University of Konstanz. He also uses this vaccination approach to investigate the effect of social stress on the immune response of mice and to test whether immunosuppression caused by stress limits the therapeutic success of immunotherapy.

Based on the results of the study, the researchers propose to transfer these promising preclinical results into clinical application. "That could have a very positive influence on immunotherapy for certain types of cancer," said Groettrup.

The therapy concept developed in this study is currently being tested by project partners in Nijmegen (Netherlands) in a first phase 1 study to find out whether it is similarly effective in humans.

Reference: Koerner J, Horvath D, Herrmann VL, et al. PLGA-particle vaccine carrying TLR3/RIG-I ligand Riboxxim synergizes with immune checkpoint blockade for effective anti-cancer immunotherapy. Nat Commun. 2021;12:2935. doi: 10.1038/s41467-021-23244-3

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