Chemoimmunotherapy
Unlike chemotherapeutic drugs commonly used in oncology, which directly attack and kill cancer cells, immunotherapy is aimed at activating the body's immunity against cancer cells.
Recently, it has been shown that the effective chemotherapeutic drug doxorubicin, in addition to the main action, enhances the immune response of patients, causing an antitumor immune response. But the toxicity and inflammatory reactions caused by doxorubicin affect not only cancer cells, but also normal cells, which limits its use for immunotherapy.
To solve this problem, a research team led by Dr. Joo Hee Ryu from the Center for Teradiagnostics at the Korean Institute of Science and Technology has developed a prodrug for immunotherapy that reacts only with cancer cells, minimizing the toxic effect on normal cells, including immune cells.
Last year, the Center for Teradiagnostics announced the development of a drug that suppresses resistance to doxorubicin in cancer cells without affecting normal cells. Dr. Ryu's research group, on the contrary, has developed a drug that is an inactive form of doxorubicin for anti-cancer immunotherapy. The new prodrug CAP (cancer-activated DOX prodrug) becomes active under the influence of enzymes present in cancer cells. Since these enzymes are not present in healthy cells, the cytotoxic and immune effects of doxorubicin do not affect them.
In mice with colon cancer, the selective accumulation of CAP-bearing nanoparticles in the tumor enhanced anti-cancer immunity without the severe toxicity, inflammatory reaction and systemic immunosuppression characteristic of doxorubicin.
Combined treatment with CAP-bearing nanoparticles with checkpoint inhibitors resulted in complete tumor regression 50% faster compared to free doxorubicin in combination with checkpoint inhibitors. At the same time, the side effects associated with doxorubicin were significantly lower in the group of mice subjected to the new chemoimmunotherapy.
The data obtained allow us to hope that the dose of doxorubicin can now be increased without fear of side effects in order to increase its effectiveness in chemotherapy. In addition, since the prodrug was developed on the basis of an already approved doxorubicin, it is expected that the process of mass production and implementation into practice will be relatively simple.
Article S.Yang et al. Cancer-activated doxorubicin prodrug nanoparticles induce preferential immune response with minimal doxorubicin-related toxicity is published in the journal Biomaterials. Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on EurekAlert: Anti-cancer immunotherapy drug with reduced side effects and increased therapeutic effects.