Engineers from the University of Houston, MIT and Harvard have developed a new mRNA-based strategy that dramatically boosts T-cell responses to vaccines—an advance that could lead to much more potent cancer vaccines and stronger protection against infectious diseases.
Unlike conventional vaccine adjuvants, which typically provide short-lived immune stimulation, the new approach reprograms immune cells from within using mRNA instructions that expand cancer-fighting T cells.
The researchers created the adjuvant using mRNA molecules that provide instructions for two immune-related genes, IRF8 and NIK, which activate key immune signaling pathways and drive immune cells into a more active state.
“In mouse studies, this mRNA-encoded adjuvant enabled the immune system to completely eradicate tumors in multiple cancer models, either alone or given together with a tumor antigen,” said Akash Gupta, assistant professor in the William A. Brookshire Department of Chemical and Biomolecular Engineering and a PRITC. Scholar, who is the first author of the study published in Biotechnology of nature. “The adjuvant also enhanced the T-cell response to influenza and Covid-19 vaccines.”
T cells play a critical role in destroying infected and cancerous cells. The researchers designed the adjuvant to enhance the activity of dendritic cells, which help activate T cells and coordinate immune responses.
Gupta conducted the research while working as a researcher at MIT’s Koch Institute for Comprehensive Cancer Research.
When these adjuvant mRNAs are included in vaccines, the number of antigen-targeted T cells is greatly increased. These T cells play an important role in clearing infected or cancerous cells.”
Daniel Anderson, a professor in MIT’s Department of Chemical Engineering and senior author of the study
In mouse studies in various cancer models, the approach generated strong anti-tumor immune responses and, in many cases, eradicated tumors. These mRNA-based adjuvants also enhanced responses to checkpoint inhibitor therapies and produced a 10- to 15-fold increase in T-cell responses when combined with Covid-19 and influenza vaccines.
“Most cancer immunotherapies rely on external signals to activate immune cells. We are taking a different approach – reprogramming immune cells from within by targeting the internal signaling machinery,” said Riddha Das, co-first author of the paper.
The researchers now plan to build on these findings by evaluating the platforms in additional models of advanced cancer translational and clinician-driven studies, with the goal of developing new mRNA-based approaches for cancer therapy and infectious disease vaccines.
The research was funded by Sanofi, the National Institutes of Health, the Marble Center for Cancer Nanomedicine, and a Koch Institute Support Grant from the National Cancer Institute.
