Gel as a skin cancer killer: Researchers have developed a new therapeutic approach against melanoma. In this case, a hydrogel enriched with bacterial components is injected into the melanoma. This gel then mobilizes the immune system against skin cancer. In tests with cell cultures and mice, this immunotherapy inhibited tumor growth and suppressed the formation of metastases in the lungs. The next step is a clinical study on humans.
Melanoma is the most aggressive variant of skin cancer. The tumors can be easily removed if they are diagnosed early and the chances of a cure are good. However, if black skin cancer is detected too late, it has often already formed metastases and the chances of survival drop drastically. The cancer is then usually treated with chemotherapy and radiation, and more recently biological inhibitors and various immunotherapies used with antibodies and other immune-activating agents. In more than half of the patients, however, the skin cancer does not respond to the usual immunotherapies.
Tuberculosis bacteria as therapy aids
Researchers are therefore looking for new treatment options. One of them is the use of the so-called BCG bacteria. This strain of the bovine tuberculosis pathogen Mycobacterium bovis, originally developed for tuberculosis vaccination, can induce immune reactions against skin cancer tumors by activating scavenger cells and dendritic cells against the cancer. So far, however, this BCG treatment has not been effective against metastases, and treatment with living bacteria is always associated with a certain risk.
That is why Mirela Kremenovic from the University of Bern and her colleagues have now developed a new variant of BCG therapy against melanoma. To do this, they embedded a solution of bacterial components Hydrogel a – a scaffold of crosslinked polymers that is liquid at room temperature but gel-like at body temperature. “Such hydrogels protect active ingredients from the environment and release them at predetermined rates,” explains the team.
Tumor growth and metastases inhibited
To test how well the BCG lysate packaged in the hydrogel works, the researchers injected mice with this active ingredient directly onto the skin cancer tumors. For comparison, a second group of mice received the conventional BCG active ingredient. It turned out that both therapies reduced local tumor growth. “However, the BCG lysate was significantly more effective than the living BCG,” report Kremenovic and her colleagues. The hydrogel therapy mobilized significantly more immune cells and immune messengers than the living bacteria.
More importantly, in the mice treated with the hydrogel, the treatment also suppressed the formation of metastases in the lungs. The immunotherapy was also effective against an injection of adenocarcinoma cells under the skin: while the control animals then developed numerous new tumors, the mice treated with the BCG lysate remained tumor-free. Overall, local injection of the BCG lysate hydrogel significantly increased the mice’s survival time, the team reports.
Clinical study planned
According to the research team, the BCG hydrogel could represent a promising new therapy option for skin cancer patients. “The BCG-Hydogel prolonged survival and suppressed metastasis formation in mice. This indicates its potential as an adjunctive therapy for patients with metastatic melanoma,” write Kremenovic and her colleagues.
“Local application of the hydrogel loaded with BCG lysate is an effective and safe immunotherapeutic option for reducing metastatic burden and prolonging survival in melanoma patients,” says senior author Mirjam Schenk from the University of Bern. In addition, the hydrogel requires less frequent injections because it gradually releases the BCG lysate.
In the next step, the researchers now want to test the effectiveness of the BCG hydrogel on humans in clinical studies. Further tests on the effectiveness of this therapy against other types of cancer are also planned. (The Journal for ImmunoTherapy of Cancer, 2022; doi: 10.1136 / jitc-2021-004133)
Source: Wilhelm Sander Foundation