Presidential Frontier Faculty Fellow, CPRIT Scholar and assistant professor of chemical and biomolecular engineering Akash Gupta has received $50,000 from the Department of Defense Congressionally Directed Medical Research Programs (CDMRP) Peer Reviewed Cancer Research Program (PRCRP) Convergent Science Cancer Consortium for his Seed Project application, “Targeted mRNA-LNPs for In Situ CAR-T Cell Engineering.”
CAR-T cell therapy — a personalized form of immunotherapy that genetically modifies some of patients’ own immune cells to fight cancer — has “transformed the treatment of several blood cancers,” said Gupta. The process, however, is complex, expensive and can take weeks; it involves removing a patient’s T cells, genetically engineering them in a specialized facility, and then infusing them back into the patient to help fight their cancer.
“Our goal is to develop lipid nanoparticles that can deliver genetic instructions directly to T cells inside the body, essentially allowing the body to generate CAR-T cells in situ,” Gupta added. “We are using messenger RNA (mRNA), which provides temporary instructions to the cells without permanently altering their DNA. If successful, this approach could provide a simpler, more scalable, and potentially safer way to generate CAR-T cells without the need for extensive laboratory-based cell manufacturing.”
Gupta’s research has focused on developing nanotechnology and mRNA-based approaches to “precisely engineer immune cells.” One of the major takeaways from this work is that the therapeutic potential of mRNA “depends heavily on our ability to deliver it to the right cells in the body.”
“CAR-T therapy is a particularly exciting opportunity because we already know that engineered T cells can be remarkably powerful against cancer. The challenge is making this therapy easier to manufacture and more broadly accessible. Ultimately, we hope this research can help make CAR-T therapy simpler, more accessible, and easier to translate to patients. We are working closely with researchers at MD Anderson Cancer Center, which will allow us to rapidly evaluate promising technologies in humanized cancer models and help accelerate their potential translation to the clinic,” he said.
While the project’s initial focus is on blood cancers, its longer-term goal is to expand this approach to develop powerful CAR-T therapies for solid tumors — an area where CAR-T treatments have so far seen more limited success. Unlocking the ability to precisely deliver mRNA to specific immune cells inside the body could provide a platform for developing many different types of cancer immunotherapies while minimizing delivery to unintended cells.
“One aspect I think is particularly important is that this project is not simply about developing another CAR-T therapy. It addresses one of the major challenges in mRNA medicine: how do we deliver genetic instructions precisely to the cells we want to reprogram inside the body?
“If we can solve this challenge, the impact could extend well beyond this individual project, said Gupta. “It could help expand the possibilities for programmable medicines, where specific immune cells can be temporarily reprogrammed inside the body to perform different therapeutic functions, while minimizing unwanted effects on other cells and tissues.”