BUFFALO, NY--Whole body hy-perthermia, similar to that of a prolonged
mild fever, results in antitumor effects that may be due to increased
immune system activity and increased induction of heat shock proteins
(HSPs). "These proteins are the primary protectors of cells
against further heat exposure and other stresses," said John
Subjeck, PhD, of Roswell Park Cancer Institute, at the first meeting
of the Regional Cancer Center Consortium for Biological Therapy of
Cancer, hosted by Roswell Park.
In murine studies, the Roswell Park researchers have determined that
whole body hyperthermia can induce tumor cell apoptosis by simulating
the thermal element of a mild fever. This tumor cell killing appears
to be due, in large part, to the increased activity of natural killer
cells. Dr. Subjeck also presented evidence that tumor vascular and
cell adhesion proteins can be affected by this treatment.
"We were somewhat surprised to learn that heat shock proteins
could be induced by very mild, low-temperature heat treatments
extended for several hours," he said. Observing that this same
mild hyperthermia treatment led to alterations in lymphocyte
cytoskeleton, uropod formation, and protein kinase C activation and
distribution, the researchers began to look more closely at various
immune system functions. "We found that all of these biological
properties and antitumor effects could be tempered by heat shock
protein production," he noted.
Focus on Large Heat Shock Proteins
Current research at Roswell Park is focused on the
large-molecular-weight families of HSPs, particularly HSP110 and
GRP170, that protect cells from damage by heat, anoxia, and other
stresses. HSP110, in particular, has the ability to recognize
denatured proteins and help repair them, and probably does so more
effectively than any of the other HSPs.
"We are quite excited about these large HSPs because almost
nothing is known about their functions, while some of the smaller
HSPs have been studied intensively," he noted. A trial is about
to begin at Roswell Park that is similar to one underway at M.D.
Anderson in the laboratory of Dr. Joan Bull. "We will test the
effects of mild hyperthermia on the immune responses and HSP
induction in patients with advanced cancer," Dr. Subjeck said.
"In the near future, we plan to combine this treatment with
other types of cancer immunotherapies."