In June of 2021, BioNTech announced the beginning of human trials for its advanced melanoma cancer treatment, BNT111. BioNTech, known for its partnership with Pfizer in creating the Pfizer-BioNTech COVID-19 vaccine, has utilized recent mRNA advancements to develop its FixVac platform. The platform specializes in the creation of mRNA vaccines for various cancers. One such vaccine, BNT111, uses mRNA technology to enable the body’s immune system to fight melanoma tumors. The vaccine yielded positive results in Phase 1 trials and has now passed into Phase 2. The Phase 2 human trials will treat one hundred twenty participants with advanced melanoma cancer. [1]
Many consider mRNA vaccines new technology, but scientists have researched this advancement for decades. The first major breakthrough in mRNA treatment was by Robert Malone in 1987, who successfully induced human cells to create proteins from the mRNA they absorbed. Scientists acknowledged his success and began to put effort into studying mRNA as a treatment for disease. [2] Now, almost thirty-five years later, the world has watched as scientists used this technology to develop two of the most widespread COVID-19 vaccines: Pfizer-BioNTech and Moderna.
mRNA vaccines work by sending mRNA through the cellular membrane into a patient’s cells. Once inside the cell, the mRNA causes a cellular response that depends on what the mRNA codes for. The mRNA in cancer vaccines typically code for an immune response that enables T-cells to attack cancerous cells by utilizing antigens. Antigens are molecules located on the surface of cells that allow the cells to “remember” harmful substances. For BNT111, the mRNA encodes for four different antigens (NY-ESO-1, MAGE-A3, tyrosinase, and TPTE) that can be found on the surface of melanoma cancer cells. The body’s T-cells attack these antigens and store them in their immunological memory. When the T-cells encounter the same antigens on the surface of a melanoma cancer cell, they destroy it. About 90% of people with advanced melanoma have at least one of these four antigens on the surface of their cancerous cells. [2, 4, 5]
The BNT111 vaccine is in its second phase of the study and must undergo more intensive testing before being approved. However, the initial results are promising. According to BioNTech’s co-founder Özlem Türeci, “BNT111 has already shown a favourable safety profile and encouraging preliminary results in early clinical evaluation. With the start of patient treatment in our Phase II trial, we are encouraged to continue on our initial path to realise the potential of mRNA vaccines for cancer patients.” [5] In the Phase 1 mice trials that finished earlier this year, there was resounding success. Of the twenty mice that were injected with the treatment, tumor growth was halted, and in seventeen there was “a complete regression” of the cancer. [7]
In the Phase 2 BNT111 trials, a portion of the subjects are receiving the drug Libtayo alongside the cancer vaccine. The drug Libtayo consists of anti-PD-1, a blocking agent that enables the immune system to attack the cancer cells. A major hurdle in cancer treatment is the ability of cancer cells to suppress the immune system. Libtayo’s blocking agent is able to prevent the cancer cells from evading immune system effects. [1, 4, 6] BioNTech hopes that when the two treatments are used in conjunction, there will be greater success in treating the cancer.
Aside from the BNT111 trials, BioNTech is researching other possible mRNA cancer treatments. Their FixVac platform is researching five different treatments including the BNT111 treatment for melanoma. BNT112 and BNT115 are both in Phase 1 of study for prostate and ovarian cancer respectively. The vaccine BNT113 is in Phase 2 for the treatment of HPV 16+ head and neck cancer. The fifth candidate, BNT116, is still in pre-clinical trials for the treatment of non-small cell lung cancer (NSCLC). [8]
With the success of the COVID-19 mRNA vaccines, it is likely that many pharmaceutical companies will utilize recent mRNA advancements to target other diseases. mRNA vaccines are not only a possible solution for cancer treatment, but also a technology that could change how we prevent and treat diseases in the future.
References
BioNTech. (2021, June 18). BioNTech Announces First Patient Dosed in Phase 2 Clinical Trial of mRNA-based BNT111 in Patients with Advanced Melanoma [Press Release]. https://investors.biontech.de/news-releases/news-release-details/biontech-announces-first-patient-dosed-phase-2-clinical-trial
Dolgin, E. (2021). The tangled history of mRNA vaccines. Nature, 597. https://doi.org/10.1038/d41586-021-02483-w
Centers for Disease Control and Prevention. (2021, March 4). Understanding mRNA COVID-19 Vaccines. Centers for Disease Control and Prevention. Retrieved October 19, 2021, from https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines/mrna.html.
American Society of Clinical Oncology. (2020). What are Cancer Vaccines? Cancer.Net. Retrieved October 18, 2021, from https://www.cancer.net/navigating-cancer-care/ how-cancer-treated/immunotherapy-and-vaccines/what-are-cancer-vaccines.
Parkins, K. (2021, June 18). First patient dosed in BioNTech Phase II trial of mRNA cancer vaccine. Clinical Trials Arena. Retrieved October 19, 2021, from https://www.clinicaltrialsarena.com/news/first-patient-dosed-in-biontech-phase-ii-trial-of-mrna-cancer-vaccine/.
Anti-PD-1: A Novel Immunotherapy. Johns Hopkins Kimmel Cancer Center. (n.d.). Retrieved October 19, 2021, from https://www.hopkinsmedicine.org/kimmel_cancer_center/cancers_we_treat/melanoma/research/anti_pd_1.html.
Weintraub, A. (2021, September 8). BioNTech reports promising data on mRNA cocktail in mouse models of colon cancer and melanoma. FierceBiotech. Retrieved October 29, 2021, from https://www.fiercebiotech.com/research/biontech-reports-promising-data-mrna-cocktail-mouse-models-colon-cancer-and-melanoma.
BioNTech. (n.d.). Explore our Pipeline. BioNTech. Retrieved October 29, 2021, from https://biontech.de/science/pipeline?platform=34.