Yeast-Based Vaccine Induces Immune
Responses and Reduces Tumor
Size in Mice
Scientists have found that vaccination with a heat-killed, non-toxic
that is genetically engineered
to manufacture a common
tumor protein can induce specific and repeated anti-tumor immune
responses in mice. Vaccination extends overall survival and
reduces tumor size in mice that have been injected with cancer
displaying the same protein that was engineered into the yeast.
Results of this research by scientists at the National Cancer
Institute (NCI), part of the National Institutes of Health,
can be found in the July 1, 2008 issue of "Clinical Cancer
"These results provide a rationale for evaluating yeast
vaccines in cancer immunotherapy studies in humans," said
study author James W. Hodge, Ph.D., in NCI’s Center for Cancer
The type of yeast used in this study, Saccharomyces cerevisiae,
does not cause disease in humans and has been used as a delivery
vehicle for antigens, which are proteins usually on the surface
of cells or organisms that stimulate immune responses. The tumor-associated
antigen made by the genetically engineered yeast in this study
is carcinoembryonic antigen (CEA). CEA is commonly found on cancers
of the colon, rectum, stomach, breast, and lung.
The current research was designed to determine the effects of
this yeast-based vaccine on tumor growth and overall survival
using colon and pancreatic cancer models. These studies demonstrated
that the vaccine can elicit both CD4+ and CD8+ T-lymphocyte responses,
which recruit help from other immune cells and then attack and
destroy cells that bear foreign or tumor-associated antigens.
Additional study findings showed that successive administrations
of the vaccine resulted in increasing antigen-specific T-cell
responses. Vaccination with the yeast-CEA vaccine at multiple
sites induced greater T-cell responses than when the same dose
of vaccine was given at a single site. Furthermore, tumor-bearing
mice vaccinated with yeast-CEA had reduced tumor volumes and
increased overall survival compared to control mice.
One of the reasons for interest in Saccharomyces cerevisiae
as a vaccine vehicle is its lack of toxicity. Besides being relatively
non-toxic, Saccharomyces cerevisiae is heat-killed before administration.
It can also be easily engineered to express one or more antigens
in large quantities, can be grown and purified rapidly, and is
very stable. In addition, its safety in humans has already been
established in several clinical trials.
In this study, the researchers performed 24 tests on mice that
received either no treatment or the yeast-CEA vaccine. They found
that body-weight measurements, blood cell counts, serum enzyme
levels, and autoimmune assays were all within the normal range
for the vaccinated mice and were similar to those of control
mice, indicating no toxicity or autoimmunity associated with
the yeast-CEA vaccine.
Since therapeutic control of cancers with vaccines is likely
to require repeated vaccine administrations to effectively activate
tumor-specific immune responses — especially when trying to
stimulate the body’s defenses against one of its own proteins
— the researchers explored whether host immune responses to
the first yeast-CEA vaccination would decrease or neutralize
the effectiveness of booster shots of the vaccine. On the contrary,
they found that repeated administration induced greater immune
have implications for use of the yeast-CEA vaccine in humans.
A potential future application of these
humans would be to vaccinate patients who have CEA-positive tumors
with yeast-CEA and measure CEA-specific immune responses. In
view of the findings described here, patients could be vaccinated
at multiple sites, targeting different lymph nodes, to maximize
immune responses against CEA. "These results thus form the
rationale for the use of yeast-CEA in immunotherapy protocols
for carcinoma patients with CEA-positive tumors," said study
author Jeffrey Schlom, Ph.D., of NCI’s Center for Cancer Research.
These studies were conducted as part of a Collaborative Research
and Development Agreement with GlobeImmune, Inc., Louisville,
Colo. GlobeImmune is a biopharmaceutical company pioneering the
discovery, development and manufacturing of targeted molecular