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Scientist spotlights potential Achilles heel of therapeutic cancer vaccines

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Therapeutic cancer vaccines have had their ups and downs. After the initial delirium brought on by the potential of the breakthrough technology peaked, the rather ho-hum response seen in the pioneering Provenge and the rapid-fire failure of other experimental therapies caused enthusiasm to wane considerably. But now that the field has caught fire again, spurring a host of companies to license in new-wave vaccines, an investigator believes he has uncovered some solid clues to help explain some of the earlier disappointments--and how to avoid them in the future.

Writing in Nature Medicine, MD Anderson Cancer Research Center Associate Professor Willem Overwijk says he wanted to explore the cancer vaccine strategy to see if he could find the Achilles heel for these new drugs. He ended up with what he called an "aha!" moment when he zeroed in on the ways that investigators equipped vaccines to work. 

The basic idea is simple enough. A therapeutic vaccine is designed to flag cancer cells for the patient's immune system, which is intended to respond with a surge in killer T cells that go after the cancer, swarming tumors. To make sure the vaccines lingered in the body, investigators often added a booster called "incomplete Freund's adjuvant" (IFA) that's a non-biodegradable oil.    

But the vaccines performed poorly. By Overwijk's account, most of the 98 completed studies of therapeutic cancer vaccines failed while 37 more are in the clinic. There has been one major approval.

The problem, says Overwijk, is that rather than swarm tumors, the therapeutic vaccine wound up attracting the killer T cells, which went after the oily IFA at the injection site rather than the tumors. And he proved it in mouse studies. The effect could be eliminated by simply switching to a saline-based solution and getting rid of the oil.

"IFA sticks around the vaccination site for up to three months, along with the antigen designed to trigger immunity against the tumor," Overwijk said in a statement. "T cells keep attacking and secreting chemokines to call for reinforcements. But it's an unkillable target; T cells can't kill mineral oil."

Moffitt Cancer Center expert Dr. Jeffrey Weber told NPR that the animal study underscores what investigators have been learning about adjuvants and warrants careful review. But, as always, a mouse is not a human, as a long lineup of investigators have found after one amazing mouse study after the next.

"One word of caution is that obviously the skin and the subcutaneous tissue of a mouse is a lot different than in a human, so it's a little hard to extrapolate," Weber told the NPR reporter. "But within the reasonable limits I have some confidence." 

- here's the release
- read the report from NPR

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