Featured Research

from universities, journals, and other organizations

Chemotherapy For Brain Tumors Is Boosted After Vaccine Targets Resistance-related Antigen

Date:
June 15, 2005
Source:
Cedars-Sinai Medical Center
Summary:
Researchers at Cedars-Sinai's Maxine Dunitz Neurosurgical Institute recently documented that chemotherapy after immunotherapy provides significantly better results than either therapy can provide alone. Now they offer an explanation for the relative effectiveness of this two-wave assault on malignant brain tumors: chemotherapy sensitivity may be dramatically increased by targeting antigens that are involved in making tumors drug resistant. Results of their study appear in the August issue of Oncogene.

LOS ANGELES (June 13, 2005) -- In the August issue of the journal Oncogene, researchers at Cedars-Sinai Medical Center's Maxine Dunitz Neurosurgical Institute describe a molecular mechanism that appears to make malignant brain tumors more vulnerable to chemotherapy after they have been treated with the dendritic cell vaccine.

This finding builds on several studies recently published by the research team. In 2003, they reported that a protein fragment previously found in melanomas also was detected in highly aggressive brain tumors called glioblastoma multiforme (GBM). The immune system recognizes the peptide, Tyrosinase-Related Protein (TRP)-2, as a foreign invader, making it a significant target for immunotherapy.

"Our findings suggest that TRP-2 could be a powerful molecule linking chemotherapy and immunotherapy," said Keith L. Black, M.D, one of the paper's authors, director of the Maxine Dunitz Neurosurgical Institute and director of the medical center's Division of Neurosurgery and Comprehensive Brain Tumor Program.

"Based on our results, it appears that we can improve chemotherapy sensitivity by targeting TRP-2 and possibly other drug-resistant related tumor antigens. This may be a significant step in the fight against brain tumors and other malignant cancers because even as we have been able to develop very powerful and targeted chemicals, tumors have often been able to outmaneuver them," said Black.

In 2004, the researchers documented that the combination of immunotherapy and chemotherapy significantly slowed tumor progression and extended survival of patients suffering from these deadly tumors. The two therapies together were able to accomplish results that neither could achieve by itself. The average length of survival was extended to about 26 months, compared to 18 months for patients who received vaccine alone and 16 months for those undergoing chemotherapy alone.

In a number of laboratory and clinical trials, dendritic cell immunotherapy had succeeded in eliciting a powerful immune response against brain tumor cells, but significant improvements in length of survival had not been realized. One theory is that the rate at which tumor cells die is too slow to keep pace with the rapid growth and mutation of tumors in the body. Similarly, chemotherapy directed against GBM has had very little effect. Even new agents specifically designed to attack the DNA of tumor cells and prevent their replication fail or became impotent as the tumor cells developed drug resistance.

Taking into account recent articles identifying TRP-2 as a contributing factor in the ability of tumor cells to mutate and resist a variety of therapeutic drugs, the Cedars-Sinai team now offers an explanation for the relative effectiveness of this two-wave, vaccine-chemotherapy assault. The first attack comes from the dendritic cell vaccine that is specially formulated to search and destroy tumor cells that contain TRP-2. It clearly launches "cytotoxic T lymphocytes," tumor cell-killing immune cells that diminish or deplete the number of TRP-2-containing tumor cells. Other GBM cells survive, however, and continue to proliferate. But because they lack TRP-2 and therefore the ability to develop drug resistance, they are vulnerable in the follow-up assault of chemicals targeting their DNA.

John S. Yu, M.D., senior author of the paper and co-director of the Comprehensive Brain Tumor Program, said lab results confirmed a strong immune response to TRP-2 in patients' blood cells after vaccination, and cells removed from tumors after vaccination had significantly lower TRP-2 expression than did those removed earlier. Furthermore, the post-vaccine tumor cells were much more sensitive to anti-tumor drugs.

"It is important to note also that four patients in our study that demonstrated a response to TRP-2, after tumor recurrence, responded to chemotherapy with what oncologists call complete responses, which means the tumors were no longer visible on MRI," he added. "This was a small initial study and it will be very interesting to see if similar results will be repeated in larger numbers." Dendritic cell vaccination, pioneered at Cedars-Sinai in the treatment of GBM, introduces foreign proteins from surgically removed tumors to dendritic cells, which are also called antigen-presenting cells because they identify foreign material for destruction by cell-killing T lymphocytes. The tumor cells are cultured with the dendritic cells in the laboratory to enable the immune cells to recognize cancer cells as targets. When the resulting "specialized" dendritic cells are injected back into the patient, they seek out remaining tumor cells and signal for the T lymphocytes to destroy them.

This study was supported in part by NIH grant K23 NS02232.



Story Source:

The above story is based on materials provided by Cedars-Sinai Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Cedars-Sinai Medical Center. "Chemotherapy For Brain Tumors Is Boosted After Vaccine Targets Resistance-related Antigen." ScienceDaily. ScienceDaily, 15 June 2005. <www.sciencedaily.com/releases/2005/06/050615061949.htm>.
Cedars-Sinai Medical Center. (2005, June 15). Chemotherapy For Brain Tumors Is Boosted After Vaccine Targets Resistance-related Antigen. ScienceDaily. Retrieved April 23, 2014 from www.sciencedaily.com/releases/2005/06/050615061949.htm
Cedars-Sinai Medical Center. "Chemotherapy For Brain Tumors Is Boosted After Vaccine Targets Resistance-related Antigen." ScienceDaily. www.sciencedaily.com/releases/2005/06/050615061949.htm (accessed April 23, 2014).

Share This



More Health & Medicine News

Wednesday, April 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Big Pharma Braces for M&A Wave

Big Pharma Braces for M&A Wave

Reuters - Business Video Online (Apr. 22, 2014) Big pharma on the move as Novartis boss, Joe Jimenez, tells Reuters about plans to transform his company via an asset exchange with GSK, and Astra Zeneca shares surge on speculation that Pfizer is looking for a takeover. Joanna Partridge reports. Video provided by Reuters
Powered by NewsLook.com
Study Says Most Crime Not Linked To Mental Illness

Study Says Most Crime Not Linked To Mental Illness

Newsy (Apr. 22, 2014) A new study finds most crimes committed by people with mental illness are not caused by symptoms of their illness or disorder. Video provided by Newsy
Powered by NewsLook.com
Hagel Gets Preview of New High-Tech Projects

Hagel Gets Preview of New High-Tech Projects

AP (Apr. 22, 2014) Defense Secretary Chuck Hagel is given hands-on demonstrations Tuesday of some of the newest research from DARPA _ the military's Defense Advanced Research Projects Agency program. (April 22) Video provided by AP
Powered by NewsLook.com
How Smaller Plates And Cutlery Could Make You Feel Fuller

How Smaller Plates And Cutlery Could Make You Feel Fuller

Newsy (Apr. 22, 2014) NBC's "Today" conducted an experiment to see if changing the size of plates and utensils affects the amount individuals eat. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

    Health News

    Environment News

    Technology News



    Save/Print:
    Share:

    Free Subscriptions


    Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

    Get Social & Mobile


    Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

    Have Feedback?


    Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
    Mobile: iPhone Android Web
    Follow: Facebook Twitter Google+
    Subscribe: RSS Feeds Email Newsletters
    Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins