Following the explosive success of mRNA vaccines against COVID-19, BioNTech is turning its attention to cancer. Their new treatment, using similar technology, has shown great promise in mice, and is now in human trials to see whether they can bring the same success. Their results have been published in the journal Science Translational Medicine. The treatment in question is called SAR441000 (BNT131) – catchy, we know. Much like the Pfizer-BioNTech vaccine, it uses messenger RNA to provide the body with instructions to make proteins. In this case, they hope to stimulate the body into creating proteins called cytokines, which can have anti-tumor effects. Cytokines are naturally generated in the body, but by supplementing them at sites with tumors, previous research has shown that they can shrink the tumors and even entirely eradicate them. However, it is not as simple as just adding the cytokines to the desired area. Cytokines have a very short half-life – they degrade in the body rapidly to stop toxicity, and so previous treatments required constant administration. This constant dosing resulted in toxic levels of cytokines within the body, creating adverse effects that halted progression into them as a cancer treatment. Instead, researchers tried to target the cytokines directly to the tumors using viral vectors, but this led to genetic issues and interference from the immune system that was undesirable. If only there was a safe way to stimulate the body into creating these cytokines at the desired place, preventing an overload of cytokines that travel throughout the body and cause problems. Enter, mRNA therapies. By inserting a cocktail of mRNA that encodes cytokines directly into the tumor, the body creates those cytokines in large quantities, ready to fend off the rapidly-growing mass of cancer cells. When BioNTech, in collaboration with Sanofi, tried this on 20 mice with melanomas, 17 mice produced enough cytokines to effectively shrink the tumors to nothing within 40 days. When it was used on mice with two different types of tumors (melanomas and lung cancer), the therapy injected into the melanomas worked to shrink them, but also traveled off-site and inhibited the growth of lung tumors as well. The experiments suggest that the new therapy may be potent against targeted tumors and any secondary tumors that may result from it disseminating. As stated above, cytokine therapies often have undesirable effects. However, this treatment left the mice with no observable adverse effects. Riding off of the success in mice, the researchers have moved quickly into human trials. There is a large phase 1/2 trial underway involving 231 participants, with preliminary data of 17 patients published in November 2020 showing no serious side-effects. For now, the treatment is targeting melanomas and specific solid tumors when used in conjunction with other therapies, but the researchers hope to target others in the future. Source
