Melanoma is the deadliest form of skin cancer, claiming 57,000 lives annually [1]. Current treatment focuses on surgery removing the cancerous tumour, followed by radiotherapy and chemotherapy [2]. However, mRNA-4157 offers a more personalised treatment option with reduced side effects and greater effectiveness [3].
Moderna and Merck have developed this novel treatment particularly for high-risk stage III/IV melanoma, which involves administering mRNA-4157 in combination with KEYTRUDA, an immune checkpoint inhibitor that targets PD-1 (Programmed Cell Death protein 1) increasing its activity towards cancer cells [3][4]. Therefore, KEYTRUDA enhances the immune response towards cancer cells. mRNA-4157 works by identifying the mutated regions of DNA in a patient’s tumour which form neoantigens. Neoantigens are a type of antigen specific to tumour cells that are a result of somatic mutations in the DNA. These are tumour specific and not normally found in healthy cells, making them ideal targets for immunotherapy [5].
This sequence of DNA encoding neoantigens can be transcribed into mRNA and amplified to be used as a prophylactic or vaccine treatment [5]. These neoantigens, which are unique to that patient’s tumour cells, can then be identified by the innate immune systems cells, like dendritic cells, which process these neoantigens and present the resulting peptides on MHC class I molecules as they are derived from endogenous antigens. This activates the adaptive immune system‘s T cells resulting in a specific T-cell response. The immune system generates a primary immune response, training the body to recognise tumour cells so it can now either go on to attack tumour cells in the body or have the immunological memory to attack these cells in the future. Due to this being a targeted immune response, there are minimal off target effects, resulting in reduced side effects [6].
In clinical trials, mRNA-4157 is provided alongside KEYTRUDA, a monoclonal antibody that binds to and blocks the PD-1/ PD-L1 pathway [4]. By doing this it prevents suppression of the immune response, enhancing the action of mRNA-4157. When used together, these drugs have reduced mortality and distant metastasis by 49% and 62% respectively [7].
While this treatment has only recently entered Phase 3 clinical trials, it has shown promising results of a future where melanoma might not be as deadly, allowing individuals to receive treatment with fewer side effects. This technology has the potential to be applied to other cancers and even serve as a preventative vaccine for high-risk individuals. With continued research, this approach could revolutionise cancer treatment and prevention worldwide.
- pmc.ncbi.nlm.nih.gov/articles/PMC8544364/
- www.cancer.gov/types/skin/patient/melanoma-treatment-pdq
- www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)02268-7/fulltext
- www.cancerresearch.org/blog/june-2024/keytruda-receives-40th-fda-approval
- www.nature.com/articles/s41392-022-01270-x
- pubmed.ncbi.nlm.nih.gov/39115419/
- www.merck.com/news/moderna-merck-announce-3-year-data-for-mrna-4157-v940-in-combination-with-keytruda-pembrolizumab-demonstrated-sustained-improvement-in-recurrence-free-survival-distant-metastasis-free-su/
Edited by Samiya Dash
Copy-edited by Bavishya Tata
