HOUSTON Cancer vaccines that attempt to stimulate an immune system assault fail because the killer T cells aimed at tumors instead find the vaccination site a more inviting target, scientists at The University of Texas MD Anderson Cancer Center report in Nature Medicine.
A common substance used in many cancer vaccines to boost immune attack betrays the cause by facilitating a buildup of T cells at the vaccination site, which then summon more T cells to help with the perceived threat.
"Vaccines stimulate production of T cells primed to attack the target cancer, and there are many T cells in the bloodstream after vaccination. We found that only a few get to the tumor while many more are stuck at or double back to the vaccination site," said senior author Willem Overwijk, Ph.D., in MD Anderson's Department of Melanoma Medical Oncology.
The result: largely unscathed tumors while an overstimulated immune response can cause lesions at the injection site. The team found that a major culprit in this failure is incomplete Freund's adjuvant (IFA), a mineral oil-based adjuvant included in many vaccines to stoke the immune response.
"IFA sticks around the vaccination site for up to three months, along with the antigen designed to trigger immunity against the tumor," Overwijk said. "T cells keep attacking and secreting chemokines to call for reinforcements. But it's an unkillable target; T cells can't kill mineral oil."
Eventually, the T cells die. "The vaccination site increasingly resembles a viral infection, with lots of damaged tissue and antigens," Overwijk said.
Switch from IFA to saline adjuvant reverses effect
"Switching to a saline-based adjuvant in a melanoma vaccine reversed the T cell effect in mice," Overwijk said, "Major accumulations of T cells gathered in tumors, shrinking them, with minimal T cell activity at the vaccination site."
Peptide antigens are available fo
|Contact: Scott Merville|
University of Texas M. D. Anderson Cancer Center