The following news item was received this morning.
Regards
John and Melissa

Stronger immune response correlates with longer survival, giving
researchers a new tool for evaluating effectiveness of experimental
therapies
LOS ANGELES (STRICTLY EMBARGOED UNTIL JULY 15, 2008 AT 12:01 A.M. EDT) –
Researchers conducting a clinical trial of a dendritic cell vaccine
designed to fight malignant brain tumors called glioblastoma
multiforme (GBM) have found a correlation between the "intensity" of a
patient's immune response and clinical outcome, according to an
article in the July 15 issue of the journal Cancer Research.
While other studies have suggested a link, this is believed to be the
first to show direct and continual proportionality between the
strength of anti-tumor responses and clinical benefits in cancer
patients. This also may be the first documentation of a definite
immune response/patient outcome correlation that can be credited to
tumor-altering therapeutic interventions.
"Fifty-three percent of patients in our study exhibited a significant
vaccine-enhanced immune response. Compared to non-responders or those
with limited responses, the vaccine responders had significantly
longer times to tumor progression and longer survival," said Keith L.
Black, M.D., chairman of Cedars-Sinai's Department of Neurosurgery and
director of the Maxine Dunitz Neurosurgical Institute. Black is one of
the article's authors.
The study also substantiates a finding previously reported by the
researchers: Dendritic cell vaccination and chemotherapy work
synergistically to improve treatment. Time to tumor progression
increased significantly when vaccination was followed by chemotherapy,
compared to vaccination alone.
"No other vaccine trial in cancer patients has shown the kind of
progressive correlation between immune responses and clinical outcomes
that we found," said Christopher J. Wheeler, Ph.D., research scientist
at the MDNSI and the article's first and corresponding author. "We
looked at whether the correlation was present after vaccination alone
or after post-vaccine chemotherapy. It was evident only after
post-vaccine chemotherapy. This leads us to believe that while T-cell
activity may not result in net destruction of the tumor it is
fundamentally changing the tumor into one that is predominantly
comprised of chemosensitive cells rather than chemoresistant cells."
The findings also appear to give scientists a way to more quickly
evaluate future vaccine-related research.
"The demonstration that the magnitude of immune response is directly
related to survival of patients gives us a very good tool or
'surrogate marker' for clinical benefit. If we can improve the immune
response of our vaccine, we can anticipate that the clinical benefit
will be improved as well. This allows us to fine-tune our vaccine in
more of a real-time way," said John S. Yu, M.D., director of Surgical
Neuro-oncology at Cedars-Sinai, principal investigator of the clinical
trial and senior author of the article.
This study centered on the immune responses of 32 patients enrolled in
a Phase II clinical trial. Seventeen patients had a significant
positive response after three vaccinations; 15 showed no such
responsiveness. Average time to tumor progression (based on when tumor
volume increased by about 25 percent on MRI scans) was about 308 days
among responders, compared to 167 days for non-responders. Average
length of survival (based on date of death or date of last contact
with surviving patients) was about 642 days (about 21 months) among
responders, compared to 430 days (about 14 months) for non-responders.
Forty-one percent of vaccine responders, compared to seven percent of
non-responders, survived at least two years. All patients in the trial
had longer time to progression and longer time of survival, on
average, than patients undergoing standard treatment without
vaccination, although their pre-vaccine disease courses were similar.
The vaccine was first used experimentally in patient treatment in May
1998, and numerous studies have been conducted to fine-tune the
therapy and combine it with other cancer-killing treatments.
Upon founding the Maxine Dunitz Neurosurgical Institute in 1997, Black
led the development of the dendritic cell vaccine because gliomas and
other cancer cells are not readily detected or attacked by the immune
system. Dendritic cells are the immune system's most powerful
antigen-presenting cells – those responsible for helping the immune
system recognize invaders.
When a tumor is surgically removed, proteins are collected, cultured
and introduced in a Petri dish to dendritic cells taken from the
patient's blood. The new, "educated" dendritic cells are then injected
into the patient where they are intended to recognize and destroy
lingering tumor cells. Patients receive three vaccinations at two-week
intervals. A fourth vaccination is given six weeks after the third.
###
Certain rights in the dendritic cell vaccine technology and
corresponding intellectual property have been exclusively licensed by
Cedars-Sinai to ImmunoCellular Therapeutics, Inc., including
subsequently-developed versions of the vaccine investigated in this
clinical study. Yu is chairman of the board of IMUC and Black
maintains an ownership interest in the company.
Citation: Cancer Research, "Vaccination elicits correlated immune and
clinical responses in glioblastoma multiforme patients," July 15, 2008.
http://www.eurekalert.org/pub_releases/2008-07/cmc-bcs070808.php