Clone Track Underpinning Study for Personalized Pancreatic Cancer mRNA Vaccine (ASGCT 2024)

Panel Co-Chairs

• Claire Evans, PhD, Ichor Medical Systems
• David Weiner, PhD, The Wistar Institute

Panel Discussion

• Eli Gilboa, PhD, University of Miami
• Mary (Nora) Disis, MD, University of Washington
• Pablo Guasp, PhD, Memorial Sloan Kettering Cancer Center (MSK)

At the recent American Society of Gene and Cell Therapy’s (ASGCT’s) 27th Annual Meeting in Baltimore, Md., which occurred May 7–11, 2024, Pablo Guasp, PhD, MSK asked himself the question, “What can we use to teach the immune system how to recognize cancer cells?” Replying, “… the neoantigen that arise from the accumulation of mutations in cancer cells can be good candidates … while a limitation is that neoantigens usually impose a restriction towards personalized treatments; therefore, we need a delivery platform that allows for modularity where we can include and exclude neoantigens based on the mutations of each individual patient. Also, we need a platform that allows us to do this in a timely manner, so we can treat patients soon after they are diagnosed. We believe that nucleic acid [developments] have been a breakthrough in this field, and in particular mRNA [messenger RNA] is showing very promising results”. Guasp then considered which patients benefit the most from this approach, stating, “If we look at vaccines against infectious agents we see that vaccines are always given in a prophylactic setting before the patient develop[s] the disease. But, paradoxically, cancer vaccines historically have been tested in patients with advanced and metastatic disease, and we think that this may not be the best scenario. We think that cancer vaccines may work best in patient with minimal disease, such as patients that had their tumors surgically resected” he averred.

MSK partnered with BioNTech and Genentech to launch the first clinical trial of personalized mRNA cancer vaccines in pancreatic cancer. The results of this trial were published in 2023 (1). In only nine weeks, patients were receiving their own individualized cancer vaccine. This happened in such a timely manner, “because of a huge collaborative effort between all the members involved in the teams, but also because mRNA allows for this quick modularity, and this speed that I was mentioning before,” Guasp said.

During those nine weeks, the patient received a single dose of anti programmed cell death ligand 1 immunotherapy with atezolizumab and then received eight priming doses of the vaccine, followed by a standard-of-care chemotherapy and a single vaccine boost dose. “We identified specific responses elicited by the vaccine in half of the patients that receive[d] the vaccine. Not only that, but response to the vaccine correlate[s] with a delay recurrence time. … We know that this is a small clinical trial with a small number of patients, but the results are promising” Guasp added.

Reference

1. Rojas, L. A.; Sethna, Z.; Soares, K. C.; et al. Personalized RNA Neoantigen Vaccines Stimulate T Cells in Pancreatic Cancer. Nature 2023, 618, 144–150. DOI: 10.1038/s41586-023-06063-y