mRNA vaccines, initially validated through the rapid development of COVID-19 vaccines, are now demonstrating significant potential in cancer immunotherapy, offering personalized and targeted therapies. With over 60 mRNA cancer vaccine candidates currently in clinical trials, the field is rapidly evolving, driven by technological advancements and a deeper understanding of tumor immunology.
Advancing mRNA Cancer Vaccine Development
Several companies are actively pursuing mRNA-based cancer treatments. BioNTech's BNT111, an mRNA vaccine encoding four melanoma-associated antigens, is designed to elicit a robust immune response in patients with advanced melanoma. In July 2024, BioNTech reported positive topline data from a Phase 2 trial of BNT111 in combination with cemiplimab, an anti-PD-1 antibody, for patients with unresectable stage III or IV melanoma who had progressed following anti-PD-(L)1 therapy. The results indicated the potential of mRNA vaccines to enhance the efficacy of existing immunotherapies by capitalizing on synergistic effects to improve outcomes for melanoma patients.
Sarah Benafif, medical oncology consultant at University College London Hospitals, noted that BNT116, an mRNA vaccine developed by BioNTech, is being investigated for the treatment of non-small cell lung cancer (NSCLC). The phase 2 trial will recruit 130 participants across seven countries, with six of the sites located in the UK. Patients enrolled in the trial will be at different stages of NSCLC lung cancer, from early stage disease before surgery or radiotherapy to stage 4 or recurrent lung cancer. According to Benafif, "The strength of the approach we are taking is that the treatment is aimed at being highly targeted towards cancer cells. In this way, we hope that in time we are able to show that the treatment is effective against lung cancer whilst leaving other tissues untouched."
Personalized Cancer Vaccines
mRNA vaccines can be tailored to individual patients by identifying mutations specific to their tumors, creating individualized cancer vaccines that target these unique mutations. This approach aims to prevent cancer recurrence after surgery by stimulating the patient's immune system to recognize and destroy any remaining cancer cells.
Moderna is also advancing its mRNA pipeline, with mRNA-4157 being evaluated in combination with PD-1 therapy for various cancer types, including melanoma, NSCLC, and cutaneous squamous cell carcinoma. Preliminary data suggest that combining mRNA vaccines with checkpoint inhibitors like pembrolizumab could improve treatment outcomes, potentially becoming a new standard of care.
In a phase 2b trial, the combination of Moderna's mRNA-4157/V940 vaccine and Merck & Co's Keytruda (pembrolizumab) reduced the risk of death or disease progression by 44% compared to Keytruda alone in patients with melanoma. Jeffrey Weber, principal investigator in the trial, stated that "These data provide the first evidence that we can improve on the rates of recurrence-free survival achieved by PD-1 blockade in resected high-risk melanoma," and that the findings also provide the first randomised evidence that a personalised, 'neoantigen' vaccine approach may be beneficial in cancer.
Market Growth and Future Outlook
The mRNA cancer vaccine market is experiencing robust growth, with industry analysts projecting significant expansion as more candidates progress through clinical trials and demonstrate efficacy. This growth is not limited to melanoma, as mRNA vaccines are being explored for breast, prostate, and colorectal cancers. Kuick Research anticipates the first commercial mRNA cancer vaccine approval by 2029.
While challenges remain, including regulatory considerations and scaling up personalized vaccine production, the potential of mRNA cancer vaccines to enhance immune responses and provide tailored treatment options offers a promising future for oncology.
