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 Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin

nachricht Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care

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: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>