Re: Chemioterapia i badania genetyczne - PROSZE o
Znalazlam ponizszy artykul (z 2004 roku)na temat terapii genetycznej
przy raku pecherza. Badania byly robione na myszach a wyniki byly
bardzo obiecujace. Nie wiem czy miedzy rokiem 2004 a 2008 byly
przeprowadzane jakies proby na pacjentach.
Novel gene therapy for bladder cancer shows strong results in animal
Main Category: Cancer / Oncology
Article Date: 08 Sep 2004 - 0:00 PDT
Gene therapy that causes the bladder to act like a "bioreactor" to
produce and secrete the anti-cancer agent interferon-alpha has shown
dramatic benefits in preclinical tests, say researchers at The
University of Texas M. D. Anderson Cancer Center.
The researchers say their findings, published in the September issue
of Molecular Therapy, suggest this gene therapy strategy holds much
promise for treating aggressive human superficial bladder cancer and
that a clinical trial is being planned.
Human bladder tumors growing in experimental mice substantially
decreased in size after two treatments with novel gene-based
therapy. There was little or no evidence of cancer cells remaining
in the bladder in many of the mice after treatment. Also, every kind
of bladder cancer cell line tested in the laboratory responded, even
cells known to be resistant to the interferon-alpha protein.
"Of course these results have been achieved in mice, not humans, but
they are very exciting," says the lead investigator William
Benedict, M.D., professor in the Department of Genitourinary Medical
Oncology. "I have never seen a potential therapy for superficial
bladder cancer that could produce such marked regression of tumors
within the bladder."
Bladder cancer is the fifth leading U.S. cancer, and "superficial"
bladder cancer - cancer confined to the lining of the bladder wall -
is the most common type, with more than 45,000 new cases each year.
Although some patients with this cancer can be cured with the
standard biologic therapy, the use of BCG, tumors will reappear in
about half of patients, and up to 30 percent of them will die from
disease. Because neither BCG nor chemotherapy can effectively
prevent a significant percentage of superficial bladder cancer from
becoming aggressive, researchers at M. D. Anderson have been
studying novel gene therapy approaches to this clinical problem.
Their work is being funded by a $13 million Specialized Programs of
Research Excellence (SPORE) grant awarded to M. D. Anderson by the
National Cancer Institute in 2001 - the only such federal SPORE
dedicated to bladder research.
The bladder has long been thought to be ideal target for gene
therapy, because it is easily accessible by catheter, and is largely
a self-contained "bag-like" organ. Benedict and his team of
researchers decided to look at use of gene therapy to deliver
interferon-alpha, an immune system modulator which can improve a
patient's natural response against cancer as well as kill cancer
cells directly. Interferon-alpha is commonly used as treatment in a
number of cancers, such as several types of leukemias, lymphoma,
melanoma, and kidney cancer. However, it has been observed that
tumor cells can become resistant to the immune protein.
To investigate alternative ways to deliver interferon, the
researchers teamed up with scientists from the San Diego
biotechnology company Canji, Inc., which is affiliated with
Schering-Plough Corporation, to evaluate recombinant adenoviruses
encoding interferon-alpha (Ad-IFN_). These modified adenoviruses can
produce high levels of interferon-alpha when they infect cells, but
are engineered to prevent virus replication. The investigators
combined Ad-IFN_ with an additional agent, Syn3, to enhance
expression of IFN in the cells which line the inside of the bladder.
Mice that were growing human tumors in their bladders received two
one-hour instillations directly into the bladder. The cells lining
the inside of the bladder, both normal and cancerous, "took up" the
Ad-IFN_, and a marked decrease in tumor size was seen. "This is a
major finding since many human bladder cancer cell lines are
resistant to the interferon-alpha protein, including the ones used
in this study," says Benedict. "In addition, there was little
One of the key advances is that the virus was able to harness cells
in the bladder to function as "biological factories, producing high
local concentrations of interferon-alpha in the bladder over an
extended time," he says. "That has never been seen before."
"The degree of effectiveness of the Ad-IFN_/Syn3 therapy was a
surprise to all of us," says Benedict. "We know that going from
mouse to man is a crucial step, but if the therapy performs half as
well in the clinic as in this preclinical study, we may well
significantly advance the care of patients with bladder cancer."
Working with Benedict on the study was, from Canji, Inc.: Robert
Connor, Ph.D., Jennifer Philopena, Heidrun Engler, D.V.M., Ph.D.,
William Demers, Ph.D., and Daniel Maneval, Ph.D.; and from M. D.
Anderson: Ziming Tao, M.D., Chang-Soo Kim, M.D., Xinqiao Zhang,
Ph.D., Jain-Hua Zhou, M.D., Ph.D., Liana Adam, M.D., Ph.D., David
McConkey, Ph.D., Angela Papageorgiou, Mark Munsell, and Colin
Contact: Heather Russell
University of Texas M. D. Anderson Cancer Center