From clinical cancer research: Rethinking Therapeutic Cancer Vaccine Trials

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?”

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.

About Therapeutic Cancer Vaccines unlike preventative vaccines, like those
that protect against human papillomavirus or the flu, therapeutic cancer
vaccines are given in the hopes of treating an existing disease. These
cancer vaccines generally fall into two categories: cell-based, where
vaccines are created using cells from the patient’s own immune system that
have been activated to the presence of cancer antigens and delivered back to
the patient along with additional proteins that facilitate immune
activation; and vector-based, where an engineered virus, or vector, is used
to introduce cancer proteins and other molecules to stimulate the immune
system. Both approaches are designed to rile the patient?s immune system
into attacking tumor cells.

In their review Schlom and his colleagues looked at two cell-based vaccines,
Sipuleucel-T (Provenge) and GVAX, as well as three trials using an
engineered pox-virus vector. While this review article focuses on prostate
cancer vaccines, the researchers consider these trials as examples of
ongoing progress in similar vaccine therapies for lymphoma, melanoma,
pancreatic, lung and other types of cancer.

Cancer Vaccines: Moving Beyond Current Paradigms,& Jeffrey Schlom, et.
al., Clinical Cancer Research, July 1, 2007, Volume 13, No. 13, pages

This release was supplied by American Association for Cancer Research
For additional information you can contact: Greg Lester at – 267-646-0554

A CNBC video about this topic can be viewed by clicking here

Joel T Nowak MA, MSW