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 'Living bandages': NUST MISIS scientists develop biocompatible anti-burn nanofibers
16.02.2018 | National University of Science and Technology MISIS

nachricht New process allows tailor-made malaria research
16.02.2018 | Eberhard Karls Universität Tübingen

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: In best circles: First integrated circuit from self-assembled polymer

For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.

In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...

Im Focus: Demonstration of a single molecule piezoelectric effect

Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale

Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...

Im Focus: Hybrid optics bring color imaging using ultrathin metalenses into focus

For photographers and scientists, lenses are lifesavers. They reflect and refract light, making possible the imaging systems that drive discovery through the microscope and preserve history through cameras.

But today's glass-based lenses are bulky and resist miniaturization. Next-generation technologies, such as ultrathin cameras or tiny microscopes, require...

Im Focus: Stem cell divisions in the adult brain seen for the first time

Scientists from the University of Zurich have succeeded for the first time in tracking individual stem cells and their neuronal progeny over months within the intact adult brain. This study sheds light on how new neurons are produced throughout life.

The generation of new nerve cells was once thought to taper off at the end of embryonic development. However, recent research has shown that the adult brain...

Im Focus: Interference as a new method for cooling quantum devices

Theoretical physicists propose to use negative interference to control heat flow in quantum devices. Study published in Physical Review Letters

Quantum computer parts are sensitive and need to be cooled to very low temperatures. Their tiny size makes them particularly susceptible to a temperature...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on High Temperature Shape Memory Alloys (HTSMAs)

15.02.2018 | Event News

Aachen DC Grid Summit 2018

13.02.2018 | Event News

How Global Climate Policy Can Learn from the Energy Transition

12.02.2018 | Event News

 
Latest News

Rare find from the deep sea

20.02.2018 | Life Sciences

In living color: Brightly-colored bacteria could be used to 'grow' paints and coatings

20.02.2018 | Life Sciences

Observing and controlling ultrafast processes with attosecond resolution

20.02.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>