Geron Corporation Reports Publication of Research Validating Telomerase Cancer
Immunotherapy
Business Editors & Health/Medical Writers
MENLO PARK, Calif.--(BUSINESS WIRE)--Sept. 12, 2002--Geron
Corporation (Nasdaq:GERN) announced today that researchers at Duke
University Medical Center have published data providing additional
validation for the use of telomerase as an antigen for cancer
immunotherapy.
The research, published in the September 1, 2002 issue of Cancer
Research, shows that RNA encoding the protein component of telomerase
(TERT RNA), when introduced into dendritic cells (DCs), is effective
in priming telomerase-specific cytotoxic T-lymphocytes (CTLs) to
target and destroy malignant tumors. The TERT RNA-modified DCs also
induced a significant "helper" T cell response, which is considered a
critical component for potent and durable cellular immune responses.
Importantly, the in vitro studies also suggest only a "minimal risk"
that telomerase immunotherapy will target the rare normal cells that
transiently express telomerase.
Telomerase is abnormally activated in all human cancer types,
including breast, lung, colon, prostate and hematologic tumors. That
makes telomerase an attractive candidate for use in a therapeutic
cancer vaccine. A Phase 1 study of Geron's ex vivo telomerase vaccine
is currently underway in patients with metastatic prostate cancer at
Duke University Medical Center.
The newly published research, performed by Drs. Johannes Vieweg,
Zhen Su, Eli Gilboa and their colleagues at Duke, builds on the
earlier work by Duke and Geron researchers, published in the September
2000 issue of Nature Medicine, which demonstrated that TERT
RNA-modified DCs generated an in vivo immune response in mice that
inhibited the growth of all malignant tumors tested, including breast,
melanoma, and bladder cancer. As announced on August 27, 2002, Geron
has received U.S. Patent No. 6,440,735 which covers the application
and commercialization of this novel approach to cancer therapy.
"These experimental results are very important," commented Calvin
B. Harley, Ph.D., Geron's chief scientific officer. "It is widely
recognized that telomerase is universally present in cancer cells, and
that an effective TERT-based cancer vaccine could be used against a
broad range of tumor types. These results demonstrate again that TERT
RNA should function as an effective immunogen in cancer patients,
stimulating telomerase-specific immune cells that can destroy cancer
cells. They also suggest that the broad immune response stimulated by
TERT RNA should lead to tumor cell death without damaging the normal
cells that express lower levels of telomerase."
Study Results
The published paper notes the findings of other research that, to
be effective, a cancer vaccine should produce both CD8+ T cells (such
as CTLs) that bind to antigenic peptides in association with MHC Class
I molecules, and CD4+ "helper" T cells that bind to antigens in the
context of MHC Class II molecules. The TERT-modified DC vaccine did
both.
The Duke scientists transfected DCs from human cancer patients
with either TERT RNA or TERT RNA modified to include the sequence
encoding LAMP (lysosome-associated membrane protein), which when
coupled with an antigen has been shown to boost "helper" T cell
response to that antigen. They demonstrated that both forms of TERT
were equally effective at stimulating a telomerase-specific CTL
response. As expected, the TERT RNA modified with LAMP demonstrated
enhanced enlistment of CD4 "helper" T cells, which is hypothesized to
result in a more robust anti-tumor immune response. Somewhat
surprisingly, the unmodified TERT RNA also showed a significant CD4
response.
The investigators used TERT RNA-transfected DCs from a cancer
patient to stimulate autologous CTLs from blood cells. The resulting
CTLs were very effective at recognizing and destroying a number of
telomerase-positive human targets, including prostate cancer cells,
colon cancer cells, liver cancer cells and breast cancer cells, while
not targeting control cells.
Although these telomerase-specific CTLs effectively lysed
(destroyed) DCs that had been transfected with either TERT RNA or RNA
from renal cancer cells, they did not lyse DCs transfected with RNA
from several normal tissues that express telomerase transiently or at
low levels, including bone marrow, normal renal epithelium, normal
skin, or adrenal gland. As reported in the paper, these and other
results suggest that the telomerase expression levels in the few
non-malignant tissues that express the enzyme are "below the necessary
threshold level to be targeted by telomerase immunotherapy." The
authors concluded that "vaccine-induced autoimmunity may not be a
serious issue with this approach."
"These preclinical results suggest that the ex vivo telomerase
vaccine should be safe," said David B. Karpf, M.D., Geron's executive
medical director. "The approach described in this paper is currently
being explored in the Phase 1 trial of the ex vivo telomerase vaccine
underway in patients with metastatic prostate cancer at Duke
University Medical Center. The paper shows the potential of this
approach for treating prostate cancer and other cancers as well."
Physicians or patients who would like more information on the Duke
telomerase vaccine trial may contact the clinical trial coordinator at
919/668-3457.
Geron is a biopharmaceutical company focused on developing and
commercializing therapeutic and diagnostic products for applications
in oncology and regenerative medicine, and research tools for drug
discovery. Geron's product development programs are based upon three
patented core technologies: telomerase, human embryonic stem cells,
and nuclear transfer. |
