Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Antibody therapy can increase the effectiveness of cancer vaccine, early studys

02.04.2003


The benefit of some cancer vaccines may be boosted by treating patients with an antibody that blocks a key protein on immune system T cells, according to a small, preliminary study led by researchers at Dana-Farber Cancer Institute and Brigham and Women’s Hospital.



The study, to be published online on April 1 in the Early Edition of the Proceedings of the National Academy of Sciences (www.pnas.org), tested the effect of a single injection of the antibody MDX-CTLA4 in nine patients who had previously been treated with cancer vaccines for either metastatic melanoma or metastatic ovarian cancer. The result, in every patient who had received a particular kind of vaccine, was widespread death of cancer cells and an increase in the number of immune system cells within the tumors – evidence of a potent immune system attack.

"This study makes a strong case that combined immunotherapy – consisting of a vaccine and antibodies – can elicit a potent immune response to some types of tumors in patients," says the study’s senior author, Glenn Dranoff, MD, of Dana-Farber.


The technique was inspired by the laboratory work of study co-author James Allison, PhD, a Howard Hughes Medical Institute investigator at the University of California, Berkeley. He and his colleagues discovered that a protein, or antigen, called CTLA-4 on T cells restrains the immune system from attacking cancer cells. In a series of laboratory and animal experiments, Allison’s team showed that combining a cancer vaccine with an antibody able to block CTLA-4 resulted in an especially potent immune attack on tumors.

On the basis of those findings, Dranoff and his colleagues launched a Phase I clinical trial of the technique in a small group of patients. Because animal experiments had indicated that giving MDX-CTLA4 in combination with a vaccine might prompt the immune system to attack some normal cells, researchers decided to give the antibody to patients who had already been vaccinated.

Seven of the study participants had metastatic melanoma, a potentially fatal cancer that originates in skin cells, and two had metastatic ovarian cancer. In all three melanoma patients who had been treated with one form of vaccine, tumors showed extensive signs of cell death and were saturated with large numbers of tumor-fighting immune cells. The same results were seen in the two ovarian cancer patients who had been treated with the same type of vaccine. (The vaccine is created by loading tumor cells with a gene called GM-CSF that alerts the immune system to the tumors’ presence, prompting an anti-tumor attack.)

Of the four melanoma patients who had received a different type of vaccine based on melanoma antigens, none experienced a similar benefit, researchers found.

While none of the study participants had serious reactions to the antibody itself, some of the melanoma patients developed a mild immune reaction against normal skin cells called melanocytes, but it was not a dangerous side effect.

Previous clinical trials have shown that vaccines can be at least temporarily effective in treating metastatic melanoma and ovarian cancer, but most patients eventually succumb to their disease. One of the reasons for this may be that the CTLA-4 molecule gradually weakens the immune system’s ability to recognize and respond to tumor cells.

"By blockading CTLA-4 with antibodies, we had hoped to strengthen the immune response produced by cancer vaccines," remarks Dranoff, who is also an associate professor of medicine at Harvard Medical School and a Leukemia and Lymphoma Society clinical scholar. "Work in the laboratory and in animal models suggested that this approach could be effective. The new study offers the first evidence that the technique has promise in human patients, although much more study will be needed to demonstrate that this is the case."

The study’s lead author is Stephen Hodi, MD, of Dana-Farber. Other co-authors were from Massachusetts General Hospital, Massachusetts Eye and Ear Infirmary, Harvard Medical School, and Mederex, Inc.



###
Funding for the research was provided in part by the Berlex Oncology Foundation, National Institutes of Health, the Leukemia and Lymphoma Society, the Cancer Research Institute, and Mederex, Inc.

Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.

Bill Schaller | EurekAlert!
Further information:
http://www.dfci.harvard.edu/
http://www.pnas.org),

More articles from Health and Medicine:

nachricht NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)

nachricht High speed video recording precisely measures blood cell velocity
15.11.2017 | ITMO University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Antarctic landscape insights keep ice loss forecasts on the radar

20.11.2017 | Earth Sciences

Filling the gap: High-latitude volcanic eruptions also have global impact

20.11.2017 | Earth Sciences

Water world

20.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>