The advent of mRNA cancer vaccine
- rohiteshgupta
- Jan 3, 2024
- 2 min read
A seed turns into a huge tree only when provided habitable environment over many years. Similar is the case in any research domain: Carefully crafted questions and creative thinking when pursued over years often result in out-of-the-box technologies driving humanity. In the context of life sciences, cancer vaccines have been researched for decades but have seen their fruit ripening only in recent years.
The US FDA-approved Sipuleucel-T vaccine was the first vaccine for cancer cure but could increase the life span only by 4 months for prostate cancer patients. With the new domain of mRNA vaccines coming up, recently, a couple of mRNA cancer vaccines targeting personalized tumors have shown success for melanoma and pancreatic cancer.
Early 2023, the US FDA granted breakthrough designation to a combination of a personalized mRNA vaccine (mRNA-4157/V940) and a monoclonal antibody towards PD-1 for the treatment of patients with resected Stage III/IV melanoma cancer. Those administered personalized mRNA vaccine encoding 34 tumor-specific antigens (neoantigens) showed 44% higher recurrence free-survival than those given PD-1 antibody alone.
Another group performed Phase 1 clinical trials using a combination of chemotherapy, a personalized mRNA vaccine, and an antibody directed to the PD-1 ligand, PD-L1 in pancreatic cancer patients. Out of 18 patients for whom personalized mRNA vaccine was designed and administered, about 8 patients showed higher T-cells towards these neoantigens and remained cancer-free after 18 months.
In both these trials, neoantigens were predicted from sequenced tumors. While these trials were based on earlier clinical trials on cancer vaccines, the success of these mRNA vaccines is currently not known mechanistically. One of the key factors is knowing the mechanism resulting in vaccine-driven T-cell expansion. This will not only help predict better neoantigens but will also help manufacture mRNA cancer vaccines focusing on similar cancer-related genetic regions. This will further help reduce its cost and amplify its reach to many patients. However, even before making this a gold standard, the long-term effects of such vaccines on self needs assessment.
A long way to go!!
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