A new cancer vaccine could boost the positive effects of existing immunotherapy drugs, increasing the success rate of treatments from 20% of cases to 75%, according to a study published in Nature Communications. The investigators found that using the vaccine in combination with an immune checkpoint inhibitor—an established immunotherapy drug with a 20% success rate overall for patients—can vastly improve the proportion of individuals who respond to treatments, eliminating tumors in 75% of cases in mice.
Immune checkpoint inhibitors stop the body's natural ramping down of its immune response, resulting in a sustained attack on tumor cells. This has proven to be effective for certain types of cancers, such as melanoma and squamous cell skin cancer, lung cancer, kidney cancer, and liver cancer. However, not all patients respond to this type of immunotherapy, with only 20% of patients with melanoma able to be cured. This is in part due to the reliance of immune checkpoint inhibitors on an existing 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 to work from.
The researchers have developed a technique that can kickstart the body’s immune response to a tumor. The microparticle-based cancer vaccine, which uses a toll-like receptor 3 (TLR3)-ligand(Riboxxim; Riboxx Pharmaceuticals). This immunostimulant has approval for use in humans, can generate the T cell response that is necessary for immune checkpoint blockade drugs to be effective.
“A major shortcoming in cancer vaccines is the availability of immunostimulants that can be used in humans,” said Marcus Groettrup, chair of immunology at the University of Konstanz, Germany, in a press release. “We can show that our clinically applicable vaccine combined with immune checkpoint blockade leads to an increase in the proportion of mice that can be cured of existing tumors to 75%.”
According to the study, mice that were injected with a single dose of the microparticle-based vaccine launched a strong antitumor immune response that was still detectable after 8 weeks. They tested the vaccine against a range of cancer protein fragments, including those of prostate cancer, breast cancer, and melanoma. Strong cellular immune responses against all these antigen fragments were obtained in mice, suggesting that the new approach might be applied to a variety of cancers.
The tumors gradually returned 30 days after vaccination because of the body's natural down regulation of its immune response. However, using an immune checkpoint inhibitor in combination with the vaccine extended the therapeutic benefits and the tumors were eliminated.
The investigators suggest these preclinical results should be transitioned into clinical application. The therapeutic concept developed in this study is currently being tested in a first, small, phase 1 clinical trial to examine whether it is similarly effective in humans.
Combining immunotherapies against cancer [news release] EurekAlert; May 18, 2021. Accessed May 20, 2021. https://www.eurekalert.org/pub_releases/2021-05/uok-cia051821.php