乳がんワクチンの効果

画像 ペンシルバニア大の最新の研究で乳がんワクチンにより転移性乳がんの生存期間が2倍に延びたという。ただし、ワクチンの効果は病気の広がりを制御しようとするもので、治癒可能なわけではない。
 Dr. Susan Domchek の研究で、転移性乳がんの19人の女性に対して、がんで過剰発現するテロメラーゼ逆転写酵素(hTERT)ペプチドと呼ばれたたんぱく質の断片を使い、最高8回の予防接種をしたところ、19人中13人はこのペプチドに反応したT細胞ができた。
 反応したT細胞ができた人とできなかった人で生存期間はそれぞれ32ヶ月と17ヶ月であった。
 乳がんワクチンの研究は30年来行われてきた。免疫反応が出た人とそうでない人がいるのはなぜなのかはわかっていない。
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Breast Cancer Vaccines Look Promising
But research still to really pan out, expert warns
By Kathleen Doheny, HealthDay Reporter
http://health.msn.com/health-topics/breast-cancer/articlepage.aspx?cp-documentid=100206004

THURSDAY, June 26 (HealthDay News) -- Women with metastatic breast cancer who developed an immune response to an investigational vaccine lived twice as long as those who didn't have an immune response, new research shows.

"If you were an immune responder, you had double the survival of a non-responder," said study author Dr. Susan Domchek, an associate professor of medicine at the University of Pennsylvania.

Her report is one of several focusing on breast cancer vaccines expected to be discussed this week at the Department of Defense Era of Hope breast cancer research meeting, in Baltimore.

"Metastatic breast cancer is treatable but not curable," Domchek said. While the ultimate hope is to cure the cancer, breast cancer vaccines are one possible way to try to control the disease's spread.

Although most people think of vaccines as shots given to healthy people to prevent infectious diseases such as measles and the flu, various cancer vaccines that have been studied for decades use cancer cells, parts of cells or substances called antigens to trigger an immune response against cancer cells already in the body.

In her study, Domchek used pieces of a protein called human telomerase reverse transcriptase (hTERT) peptide to vaccinate 19 women with breast cancer that had spread. The peptide is nearly universally overexpressed in human cancers and is recognized by certain T-cells in the body's immune system.

At the start of the study, the women had no measurable T-cell response to hTERT. After up to eight vaccinations with the hTERT peptide, however, 13 of the 19 women made T-cells that reacted to the peptide.

"We biopsied the patients' breast cancer and saw that we could see these T-cells in the tumors themselves," she said. "And, in some cases, we could see evidence of tumor cells' death."

"Those who responded lived significantly longer," she said. "People who responded lived 32 months versus a median of 17 [for those who did not respond]. Three of the women who were responders have lived more than three years."

Among the questions that remain, however, said Domchek, is this: "Were those women going to do well no matter what we did? Is immune response just a marker for a healthier patient?"

Other research on breast cancer vaccines expected to be presented at the meeting include:

* A study that focused on breast cancer patients with HER-2-positive tumors (for whom relapse is common after treatment) treated with a combination of vaccine plus an anti-cancer drug. Dr. Lupe Salazar, an assistant professor of medicine at the University of Washington, in Seattle, and her team sequenced the HER-2 protein and put pieces of it into a vaccine. They gave it to patients, along with the anti-cancer drug Herceptin. The combination helped to generate significant levels of T-cell immunity specific to the HER-2 cells, she said. As of now, "all eight [women] have done this," she said. The study will eventually include 52 women.
* A study that uses immunostimulatory peptides as a vaccine looked at the best way to deliver them. Dr. Davorka Messmer, an assistant project scientist at the Moores Cancer Center at the University of California San Diego, and her team tested a vaccine using nanoparticles loaded with the HER2 peptide that carry an immune system-stimulating peptide, called Hp91, on the outside or the inside. "We found it more potent if the immunostimulatory peptide was put on the surface of the nanoparticle," he said. The study was conducted in animals.

While breast cancer vaccines have been studied for at least 30 years, they have yet to make a real difference in the lives of patients, said Dr. Len Lichtenfeld, deputy chief medical officer of the American Cancer Society. That's not to say they won't someday, he added.

"When you look at the theory, it makes sense," he said. "The bottom line is, we are getting there, but [we're] not there yet."

Many questions remain, he said, such as "why some patients have immune responses, and others don't." It is likely, he said, that some of the vaccines will be specific to one cancer, and others may work on more than one type of cancer.

More information

To learn more about breast cancer vaccines, visit the breastcancer.org.
content by:
Healthday
SOURCES: Len Lichtenfeld, M.D., deputy chief medical officer, American Cancer Society, Atlanta; Susan Domchek, M.D., associate professor, medicine, University of Pennsylvania, Philadelphia; Lupe Salazar, M.D., assistant professor, medicine, University of Washington, Seattle; Davorka Messmer, Ph.D., assistant project scientist, Moores Cancer Center, University of California, San Diego; June 25-28, 2008, presentations, Era of Hope meeting, Department of Defense Breast Cancer Research Program, Baltimore

Copyright © 2008 ScoutNews, LLC. All rights reserved.

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Helping the Immune System Fight Cancer
http://www.breastcancer.org/tips/immune/helping.jsp

Page last modified on: June 24, 2008
Vaccines to fight cancer

A vaccine is a very common way of building up the immune system to fight infection. Using vaccines to fight breast cancer is relatively new, however, and still considered experimental. A vaccine for breast cancer may consist of an antigen cocktail of weakened or essentially dead elements of breast cancer cells that could stimulate an antibody response. The cancer vaccine might be prepared from your own deactivated cancer cells, or from extracts of breast cancer cells cultivated in a laboratory. Vaccines like this are only available in clinical trials. But as soon as these vaccines are proven effective and win FDA-approval, they will become available outside of clinical trials.

The vaccine is given by injection (usually under the skin). Once your immune system becomes aware of the antigens in the vaccine, it responds by making antibodies. Hopefully these antibodies will able to attack and destroy any remaining cancer cells. Later, if any new cancer cells appear, the circulating antibodies of the vaccine-educated immune system would destroy them also.
The challenges of cancer vaccines

Although vaccines have a strong track record in fighting many serious infections (such as polio, mumps, and measles), they are very much in the experimental stage for cancer. One problem is the way cancer progresses. It begins when one of your normal cells becomes abnormal and starts multiplying out of control, generation after generation. Each generation produces variations.

Eventually the cancer has countless faces, with a limitless variety of antigens that need to be targeted by antibodies. The cancer vaccine, however, results in a LIMITED number of antibodies against the specific cancer cell antigens that were in the ORIGINAL vaccine preparation. These antibodies may not be effective against the full range of newly developing cancer cells.

In addition, an effective vaccine must summon antibodies that target the bad cells and leave normal cells alone. The trick is to catch the cancer cells as soon as they form, and make the vaccine with cancer cell parts that are NOT shared by normal cells.

Researchers are investigating ways to identify cancer cells at this very early stage. This could be done perhaps with chemicals that would tag the problem cells, and then alter them enough so that the immune system perceives them as abnormal and attacks them.
Antibodies to fight cancer genes

Another approach is to produce antibodies against specific cancer genes called oncogenes. Normal oncogenes keep cell growth under control and suppress cancer by directing the production of a host of special proteins that conduct business as usual around the cell. Abnormal, malfunctioning oncogenes, however, such as a faulty HER2/neu gene, fail to regulate cancer cell growth, resulting in tumors. These abnormal cancer genes or their related proteins provide a very precise target for an antibody. If the abnormal gene is only found in your cancer cells, and not in your normal cells, the antibody can do a good job destroying cancer cells, leaving the rest of you alone.

An antibody therapy directed against the protein made by the oncogene HER2/neu, for instance, is Herceptin (chemical name: trastuzumab). While many of your tissues normally have HER2/neu present, it is in tiny amounts. Cancer cells that have too much HER2/neu protein around are bombarded by the Herceptin antibody (much, much more than any normal tissue). This therapy represents a remarkable advance for women with HER2/neu–positive cancers, because it effectively treats the cancer with very few side effects to normal tissue.

Another version of this approach is to deliver antibodies with attached poisons, such as nitrogen mustard or a radioactive agent, which helps kill the cancer cells. Studies of this technique in animals are encouraging, and clinical trials are ongoing.

You might be reading this section and thinking, "Wow, this stuff sounds great, why isn't this used more often? How come they haven't perfected it already?" We agree: antibody therapy holds great promise. But there are two serious obstacles with the use of antibodies to target cancer cells. First, the size of the antibodies is important relative to the size of the cells. Some cancer cells are destroyed only if the antibody molecules can penetrate the cells' outer (and sometimes inner) barriers. If they're too big, the antibodies may not be able to get INTO the cells. The second problem is that with each generation of cancer cells that form, it's hard to make antibodies that work effectively against all of the different kinds of cells that make up the cancer. Ongoing research will, it is hoped, overcome these problems.
Boosting T-cell activity

Other research is looking for ways to boost T-cell activity against antigens so that the T-cells and other fighting cells work even harder and longer to find and destroy all cancer cells.

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