Encouraging Results for Personalized Vaccine plus Checkpoint Inhibitor in Pancreatic Cancer

“Neoantigens” that are unique to tumor cells are recognized by the immune system: Immune checkpoint inhibitors (ICIs) unleash an immune attack against those neoantigens. Unfortunately, ICIs perform poorly against pancreatic cancer because these cancer cells have relatively few neoantigens.

To try to boost immune recognition of pancreatic cancer neoantigens, investigators resected pancreatic tumors from 16 people, sequenced DNA and RNA from each tumor, and determined each tumor's neoantigens. Then, they created “personalized” mRNA vaccines (like the vaccines used against SARS-CoV-2) that would cause each patient to make his or her tumor's neoantigens in abundance. Each patient received an ICI, followed by the personalized vaccine, followed by chemotherapy. In eight patients, cytotoxic CD8+ T cells were produced that attacked one or more neoantigens. In each of those patients, no evidence of residual cancer was found at 18 months. In contrast, when the personalized vaccine did not produce such CD8+ T cells, residual cancer remained. In one patient, the therapy might have eradicated not just the primary tumor but also micro-metastases.