A clinical trial of the concept is expected to open later this year led by Craig Singluff Jr., M.D., professor of surgery at the University of Virginia Medical School, and Patrick Hwu, M.D., chair of MD Andersons Department of Melanoma Medical Oncology.
Overwijk and colleagues noted 98 federally approved U.S. clinical trials of vaccines against a variety of cancers have almost all failed, while another 37 trials are open, enrolling patients. The U.S. Food and Drug Administration has approved only one therapeutic vaccine, for treatment of prostate cancer, out of all of those trials.
"Our group and many other researchers have been trying for years to improve the performance of cancer vaccines, to no avail," Overwijk said. "People kept trying because of these beguiling T cell levels in the blood. But our data suggest that the very nature of IFA-based vaccines may make it almost impossible for them to work well."
In past experiments and clinical trials, tumors were rarely examined for evidence of T cell penetration. In people, they are often inoperable, and there was no indication that it needed to be done. "But a few researchers did analyze human tumors for T cell infiltration and largely found what we found in our mouse experiments," he said.
Mouse studies reveal vaccine self-sabotage
The team studied the fate of melanoma-specific CD8-positive T cells after vaccination with the gp100 peptide with and without IFA.
Both vaccines increased levels of the desired T cells in the blood, but with IFA, the T cells dropped to nearly undetectable levels after three weeks and did not rebound even with an engineered virus-based booster. The vaccine-lacking IFA produced similar peak amounts of the T cells, a response that persisted over time.
The research team fluorescently tagged T
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center