From Clinical Cancer Research: Rethinking Therapeutic Cancer Vaccine Trials

PHILADELPHIA -- Ongoing therapeutic cancer vaccine trials have yet to show evidence of vaccines spurring a patient’s immune system to shrink tumors -- yet patients who receive these vaccines in trials tend to live longer and respond better to subsequent treatment. In the July 1 issue of Clinical Cancer Research, a journal of the American Association for Cancer Research, a team of National Cancer Institute researchers asks a fundamental question: are we looking at cancer vaccine trials the wrong way?

“Cancer Vaccines: Moving Beyond Current Paradigms,” Jeffrey Schlom, et. al., Clinical Cancer Research, July 1, 2007, Volume 13, No. 13, pages 3776-3782.

In a review of five prostate cancer vaccine trials, NCI researchers offer evidence that patients who receive vaccines may respond better to subsequent chemotherapy or hormone treatment. The specific results - or endpoints - of these clinical trials, however, were not the long term survival of patients, but rather the degree to which the vaccine caused tumors to shrink. According to the researchers, since they didn’t achieve their primary endpoints, these vaccines may be abandoned as dead-ends, despite their real therapeutic value in terms of prolonging patient survival.

“Clinical data are providing evidence that patients are living longer following vaccination, despite the fact that trials do not show the vaccines can induce the immune system into shrinking tumors,” said Jeffrey Schlom, Ph.D., chief of the Laboratory of Tumor Immunology and Biology at the National Cancer Institute. “The data suggests that the scientific community and regulatory committees ought to rethink the design of clinical vaccine trials and our current approach to measuring the effectiveness of a cancer vaccine.”

According to the researchers, it may be more helpful to think of the effectiveness of a vaccine in terms of the response of the patient, rather than the response of the tumor. While the Response Criteria in Solid Tumors (RECIST) experimental standards works well in evaluating therapies that are toxic to tumors, such as radiation or chemotherapy, they are less capable of measuring the more subtle systemic effects of immune response, Schlom said.

While there is no conclusive evidence to explain why a vaccine may lead to better patient survival, Schlom believes the evidence suggests that vaccines are, in fact, priming the immune system. “Vaccines are not passive, they induce a dynamic process of immune response that, in many cases may keep the tumor in check and enhance the effectiveness of subsequent therapies,” Schlom said.