The history of cancer vaccines is littered with candidates that showed great promise in the lab, only to flunk clinical trials. Now, scientists think they know why--the vaccines are self-sabotaging.
U.S. researchers came to the conclusion in a paper published in Nature Medicine after looking at T-cell targeting in mice. They found that instead of destroying tumors, the T-cells accumulated at the vaccination site. The paper blames the mistargeting on incomplete Freund's adjuvant (IFA), a peptide used in cancer vaccines to boost the immune response.
While IFA succeeds in increasing T-cell activity, it also appears to draw their attention away from the tumor. "The body doesn't know how to deal with the mineral oil [in IFA], and the body cannot get rid of that big blob of vaccine ... that sits under the skin. The T-cells go back and try to kill the oil, but they can't," study author Willem Overwijk, an assistant professor at MD Anderson Cancer Center in Houston, Texas, told NPR Shots. The finding could explain why T-cell activity can fail to correlate with efficacy.
Of course, just as a vaccine can show promise in the lab only to fail in the clinic, the conclusions reached about IFA in mice may not translate to humans. The IFA study looked at activity around the skin and subcutaneous tissue--areas that differ considerably in mice and humans--so a question mark hangs over the conclusions.
Overwijk now plans to tackle these doubts by running a clinical trial of a saline or water-based cancer vaccine later this year. Removal of IFA should overcome the potential T-cell distraction problem but throws up new complications too. The strength of IFA is its effectiveness at kick-starting the immune system. Switching IFA for saline could cause cancer vaccines to fail for a different reason, namely because the immune response is too weak.
- here's the Nature Medicine abstract
- check out the NPR article