Researchers from Johns Hopkins Kimmel Cancer Center managed to reduce pancreatic cancer tumors in mice using PancVAX, an immune system booster vaccine, alongside two checkpoint inhibitors. Their approach led to a better response to therapy by converting T cell-poor tumors into tumors that are rich in specific T cells.
T lymphocyte, a subgroup of white blood cells which play an important role within the immune system, are commonly depleted in pancreatic and other kinds of cancers with fewer genetic mutations. This is why the team focused on immunotherapy drugs that boost T cells. While individually they draw only a weak response, in combination they appear to work far better.
“We have already seen some promise with current vaccines being tested in patients with this cancer”, noted Elizabeth Jaffee, M.D., senior author of the study. “We now have the next generation of vaccines that are more specific to each patient’s own cancer, and we have reason to hope that a combination drug approach will offer more to patients.”
PancVAX, was created utilizing whole-exome sequencing, RNA sequencing (RNASeq), and an in silico immunogenicity prediction algorithm, NetMHC, to generate the neoantigen-targeted vaccine. The two checkpoint drugs were derived from anti-PD-1 and agonist OX40 antibodies.
“The vaccine tunes in the signal of the tumor for therapy, and the checkpoint drugs amplify the signal to teach the immune system to go after the tumor”, explained corresponding author Neeha Zaidi, M.D. “This framework is a personalized strategy to go after pancreatic and other nonimmunogenic cancers”.
Findings were published by The Journal of Clinical Investigation in a study detailing how after the treatment cleared the tumors, the reintroduction of mutated cells did not lead to the development of new growths.
The approach holds significant promise for patients who are or become resistant to immunotherapy drugs after a recurrence of their tumors.