Study led by MCC researchers presents promising alternative to viral vectors for cancer immunotherapy

Research led by the Masonic Cancer Center's Branden Moriarity and Beau Webber, co-directors for MCC's genome engineering shared resource, has the potential to push cancer treatment into a new era by introducing an innovative non-viral approach to enhance adoptive cellular therapy. The study published in Nature Biomedical Engineering unveils a genetic engineering method that avoids the cost and safety concerns associated with viral vectors—tools used in genetic engineering—potentially transforming cancer immunotherapy.

This study opens the door for a future where treatments are more accessible to patients in need, making the process simpler and less costly while elevating safety and efficacy standards.

"Our optimized methodology has the potential to significantly advance the landscape of adoptive cellular therapy, offering a near-term alternative to viral vectors," said Branden Moriarity, an associate professor at the U of M Medical School and senior author of the study.

By combining the precision genome editing technology CRISPR-Cas9 and a novel DNA integration mechanism, the research team successfully integrated large DNA sequences into human T-cells in a site-specific fashion at efficiencies nearing that of viral vectors. The function of the engineered cells was at least as effective as viral methodologies used to produce commercial CAR-T—an immunotherapy that uses your T-cells to make your treatment—but with reduced potential for harmful effects observed with viral vectors that insert at random locations in the genome. Additionally, they found that engineered CAR-T cells worked well against tumors in both test tubes and living organisms. The method also aligns with Current Good Manufacturing Practice (CGMP) regulations established by the U.S. Food and Drug Administration (FDA), making it well-suited for broad adoption in clinical settings.

“There is a strong interest in non-viral methods for T-cell engineering that avoid the cost, complexity, and safety risks of viral vectors; however, to date, other non-viral methods have been limited by efficiency and the size of DNA cargo that they can integrate at precise locations in the genome. Our current study overcomes these limitations,” said Beau Webber, an associate professor at the U of M Medical School and lead author of the study.

The traditional reliance on viral vectors for engineered immune cells has brought challenges like high costs, regulatory obstacles, and safety concerns. This research avoids these challenges and ensures improved safety, effectiveness, and scalability in generating genetically engineered T-cells for cancer treatment. It holds promise for addressing challenges in other fields requiring immune cell engineering, such as infectious diseases and autoimmunity.

The research team is currently focused on the near-term clinical application of this technology and has ongoing collaborations to translate this technology to the clinic in 2024.  

This research was funded by an ongoing research partnership with Intima Bioscience. 

This article was written by Ezra Xiong, U of M Medical School, and first appeared on the U of M Medical School website.