A research team from the Medical University of Vienna, led by Maria Sibilia, has investigated a new combination cancer therapy. This therapy employs the systemic administration of the tissue hormone interferon-I combined with the local application of Imiquimod. This combination showed promising results in topically accessible tumors such as models of melanoma and breast cancer: the therapy caused the death of tumor cells at the treated sites and simultaneously activated the adaptive immune system to combat even distant metastases. The results published in the most important journal. nature cancer could improve the treatment of superficial tumors such as melanoma and breast cancer.
In recent years, immunotherapies have had significant success in the treatment and cure of a wide range of cancers. However, for some patients these agents are still not effective enough. Maria Sibilia, Director of the Cancer Research Center at the Medical University of Vienna, investigated the effects of a combination immunotherapy consisting of the systemic administration of the tissue hormone interferon (IFN)-I and the local with imiquimod. . Imiquimod is an active substance that activates the innate TLR7/8 receptors and is used to treat basal cell carcinomas. The researchers used several preclinical tumor models of melanoma and breast cancer in mice. What both tumors have in common is that they are accessible to local therapy and often form distant metastases.
Effective for local tumors and distant metastases.
Immunotherapies use the body’s own immune system to fight cancer cells. Plasmacytoid dendritic cells (pDCs), which are activated by Imiquimod through TLR7/8, play an important role in this process. The study demonstrated that oral imiquimod stimulates pDCs to produce the tissue hormone IFN-I. This sensitized other dendritic cells and macrophages in the tumor environment to topical imiquimod therapy, which inhibited the formation of new blood vessels through the cytokine IL12, leading to tumor cell death. The combined immunotherapy not only had an effect on the treated tumors, but also on distant metastases. It reduced the formation of new metastases, thus preventing tumor relapses and increasing the sensitivity of melanomas to checkpoint inhibitors.
“These findings illustrate that the combination of systemic treatment with imiquimod or IFN-I and topical therapy with imiquimod has the potential to expand treatment options for patients and improve therapy outcomes in locally accessible tumors such as melanoma or cancer. of breast”, emphasizes María Sibilia. “Topical treatment of the primary tumor with imiquimod is essential for this combination therapy with systemic IFN-I to be effective at the treated site and also to eliminate distant metastases,” adds Philipp Novoszel, MedUni Vienna, one of the first authors of the study. .
The results suggest that this therapeutic strategy has the potential to improve treatment results in superficial and, therefore, locally accessible tumors, such as melanoma and breast cancer, on the one hand through the death of cancer cells associated with the therapy. in locally treated tumors, but also by inducing a T cell-induced antitumor immune response in distant metastases, which is further enhanced by checkpoint inhibitors.
“Our goal is to further develop immunotherapeutic strategies to improve the long-term outlook for patients who do not yet respond well to these agents,” says Maria Sibilia, who is also deputy director of the Comprehensive Cancer Center at MedUni Vienna and the University Hospital of Vienna. .
“Since systemic interferon is a well-known anticancer therapy and dendritic cells are activated in a similar way to our preclinical models, we believe that the new combination therapy may show an effect in patients,” adds Martina Sanlorenzo, dermato-oncologist at MedUni. Vienna. and co-first author of the study.