Good news! Cancer is history (soon), one cancer at a time!
"Yale researchers have developed a new vaccine that does double duty against a rare and aggressive skin cancer, by targeting the protein essential to tumor cell growth and by adding a key signal to boost the immune system response ...
The mRNA vaccine directed the immune response to target viral large T antigen, a protein, and co-encoded interleukin-7 (IL-7), a molecule essential for the proliferation of immune cells, to enhance T cell responses, which led to increased immunity and a more durable anti-tumor response in Merkel cell carcinomas (MCC), often caused by a virus. The vaccine demonstrated potent effects in both animal models and patient samples and improved effectiveness when IL-7 was added. ...
By adding IL-7 to the vaccine, the researchers aimed to strengthen T cell response leading to better T cell expansion, improved tumor control, and memory formation. Memory was a particular focus because the aging population most at risk for MCC has an increased dependence on T cell memory, compared with younger patients, for durable T cell responses.
The study found that, in animal models, the vaccine worked well with anti-PD-1 immunotherapy, meaning it could be beneficial in other treatment scenarios including before and after surgery or in combination with other systemic therapies for metastatic disease. ..."
From the highlights and abstract:
"Highlights
• mRNA vaccines against an essential Merkel cell viral oncoprotein enhance immunity
• Vaccination is effective in mouse models and Merkel cell carcinoma patient samples
• Antigen loss limits efficacy in mouse models but not in MCC patients
• Co-encoded IL-7 mRNA boosts antigen-specific T cell memory and vaccine efficacy
Summary
Although mRNA technologies have reinvigorated cancer vaccine development, the identification of strong antigens with consistent tumor cell expression and generation of durable antigen-specific CD8+ T cell memory remain key challenges. We identified the Merkel cell carcinoma (MCC) large T antigen (LTA) as an optimal vaccine target, essential for tumor cell survival and immunogenic in a cancer with high unmet clinical need.
We developed an mRNA vaccine to MCC-LTA in murine studies and patient samples. We showed that antigen loss develops rapidly and causes resistance in mouse models when immunogenic, but non-essential antigens are targeted.
To improve T cell response durability, we co-encoded LTA and IL-7, co-localizing proliferative and memory signals spatially and temporally with antigen exposure. IL-7-containing mRNA vaccines improved antigen-specific T cell expansion, memory differentiation, and tumor control.
We propose that the principles of antigen essentiality and memory signal co-encoding may be adapted to improve the efficacy of mRNA therapeutics."
Graphical abstract
No comments:
Post a Comment