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Old 01-12-2005, 02:22 PM   #1
Susan M
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Does anyone know if the integrin mentioned AvB3 applies to HER2?

Human Body Makes Antibodies That Recognize Metastatic Breast Cancer Tumors
NewsRx.com
http://www.cancercompass.com/cancer-news/1,8347,00.htm

January 6, 2005

excerpt....
"Breast cancer cells display the high-affinity form of a particular integrin on their surfaces. This integrin, called AvB3, allows the tumor cells to interact with proteins in the bloodstream. Once bound, these proteins can form molecular bridges between the tumor cells and blood platelets, and the tumor cells can use these bridges to attach to new tissues where they can establish new tumors.

However, if antibodies such as those discovered by the Scripps Research scientists are present, they may block this process.""



A team of researchers at the Scripps Research Institute in California has reconstructed the "fossil record" of the immune systems of a group of human cancer patients to investigate if they had ever produced antibodies against their disease.

Just as a paleontologist's fossil record suggests interactions of plants and animals that inhabited earth millions of years ago, the fossil record of a cancer patient's immune system may provide a glimpse of how people's immune system interacts with pathogens and cancerous tumors today.

What this record shows is that the human body is capable of making numerous antibodies that have the ability to recognize metastatic breast cancer tumors. The Scripps Research team found several antibodies within the library constructed from the cancer patients that target a surface protein, which breast cancer cells use to metastasize. Significantly, two of the antibodies they found had evolved quite sophisticated targeting mechanisms.

When tested in mouse models, both of these anti-tumor antibodies blocked the ability of human breast cancer cells to metastasize and they helped to extinguish breast cancer that had already spread. This finding is highly significant because of the potential for using such antibodies as a new way to treat cancer.

The work of the Scripps Research team gives hope that antibodies that were originally produced by cancer patients may help to block cancer spreading and interfere with already existing metastatic disease. Moreover, the disease-fighting ability of antibodies taken from patients with cancer suggests that the immune system has a natural defense mechanism against cancer cells and perhaps can even maintain an active "immune surveillance" against cancer cells.

"People have talked about immune surveillance for 40 years," said Scripps Research President Richard A. Lerner, who is Lita Annenberg Hazen Professor of Immunochemistry, Cecil H. and Ida M. Green Chair in Chemistry, and an investigator in The Skaggs Institute for Chemical Biology at the Institute. "The fossil record suggests that we fight cancer every day."

Associate professor Brunhilde Felding-Habermann, who led the research added, "It is possible that many of us, at some point in time, have malignant cells in our body, but that we don't notice them because the immune system eliminates them before they can establish symptomatic cancer."

Also called immunoglobulins, antibodies are proteins produced by immune cells that are designed to recognize a wide range of foreign pathogens and unhealthy cells, such as those in tumor masses. They alert the immune system to the presence of the invaders and attract lethal "effector" immune cells. Scientists have reasoned that the immune system may be able to eradicate tumors successfully by producing the right antibodies.

To see if such antibodies could be found, Felding-Habermann, Lerner, and their colleagues took blood samples from 20 cancer patients, 5 of whom had breast cancer, and generated the record of their antibody immune response through a technology called combinatorial antibody libraries.

To find antibodies produced by cancer patients that bind selectively to the most dangerous subset of cancer cells, those that cause metastasis, the researchers created a combinatorial antibody library to select from among billions of protein variants for those that bound to a particular target.

They found that several of the anitbodies bound to a protein on the surface of the cancer cell called integrin AvB3. Integrins can enable cancer cells to hook onto new tissues and remain in place, rather than get flushed along in the circulatory system.

Breast cancer cells display the high-affinity form of a particular integrin on their surfaces. This integrin, called AvB3, allows the tumor cells to interact with proteins in the bloodstream. Once bound, these proteins can form molecular bridges between the tumor cells and blood platelets, and the tumor cells can use these bridges to attach to new tissues where they can establish new tumors.

However, if antibodies such as those discovered by the Scripps Research scientists are present, they may block this process.

"Cancer patients can produce antibodies that may very actively interfere with metastasis," said Felding-Habermann. One way that the antibodies can do this is by recognizing and binding to the activated form of integrin AvB3, blocking the integrin from attaching to platelets and preventing the cancerous cells from arresting in the bloodstream and invading new tissues.

Significantly, two of the antibodies the scientists discovered target the active form AvB3 integrin through its characteristic motif known as "RGD," which refers to the characteristic triad of amino acids arginineglycineaspartic acid. The finding that the discovered antibodies mimic natural ligands of integrins, but at the same time display a much greater specificity, is a remarkable example of convergent evolution: Humans and other mammals evolved the AvB3 integrin binding motif over millions of years of evolution, and the antibodies reached the same motif through a much faster evolution-in mere years or less. This demonstrates the power of the immune system to evolve a best-fit solution over the lifetime of an individual.

The research was published in the December 7, 2004, Proceedings of the National Academy of Sciences (Combinatorial antibody libraries from cancer patients yield ligand mimetic RGD cointaining immunoglobins that inhibit breast cancer metastasis. PNAS, December 7, 2004).

The work was supported by funds from the U.S. National Institutes of Health, the U.S. Army Breast Cancer Research Program, the Skaggs Institute for Research, and the Stein Endowment Fund. This article was prepared by Biotech Week editors from staff and other reports.

© 2004 NewsRx.com. All Rights Reserved. ©Copyright 2005, Biotech Week via NewsRx.com & NewsRx.net
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Old 01-12-2005, 07:04 PM   #2
Eccles
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I will be on the look-out for an answer to your question. Just wanted to thank you for bringing this article to light. FASCINATING. My position vis a vis my BC is not much different from earlier positions regarding any other health issues: ('fighting' is not for me) I look for ways to work WITH my body and all its potential. (On the more challenging days, I try to 'detach'. )
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Old 01-14-2005, 10:32 PM   #3
Lolly
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I agree, fascinating, and also very timely as I'm heading into a clinical trial for the Her2 Vaccine. Thank you Susan, and I will ask about the integrin in Seattle.
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Old 02-25-2005, 09:18 PM   #4
mamacze
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Lolly,
Did you remember to ask Dr. Salazar about the integrin? what was her read on this?
Love Kim (from CT)
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Old 02-26-2005, 10:40 PM   #5
Lolly
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Kim, I totally forgot~I won't be seeing her next time. I'll try to remember to ask the doctor-in-charge, if chemo brain doesn't win out again:)

Love, Lolly
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