Featured Research

from universities, journals, and other organizations

Antisense Treatment Promising For Deadly Brain Tumors

Date:
April 17, 2001
Source:
Jefferson Medical College
Summary:
Researchers at Jefferson Medical College have used DNA therapy known as antisense to treat patients with usually fatal brain tumors. The majority of patients treated to date have had partial responses, and one has even recovered well enough to take up golf again.

Researchers at Jefferson Medical College have used DNA therapy known as antisense to treat patients with usually fatal brain tumors. The majority of patients treated to date have had partial responses, and one has even recovered well enough to take up golf again. While most have relapsed since their initial treatment, the doctors hope the therapy will eventually be further developed and help provide patients a better quality of life.

David W. Andrews, M.D., associate professor of neurosurgery; Renato Baserga, M.D., distinguished professor of microbiology and immunology and deputy director of Jefferson’s Kimmel Cancer Center; Robert Aiken, M.D., associate professor of neurology, all at Jefferson Medical College of Thomas Jefferson University in Philadelphia and their colleagues treated 12 patients who had either glioblastoma or anaplastic astrocytoma, both deadly brain cancers, and who had failed prior therapy. In a Phase I trial, which is designed only to answer questions of drug safety, eight patients (three were treated twice) unexpectedly improved, meaning some of their tumor shrank in size, including two patients whose tumors temporarily “disappeared.”

The therapy entails using antisense against the type-1 insulin-like growth factor receptor, or IGF-1R, causing a biologically programmed death of tumor cells by a process called apoptosis and at the same time stirring the immune system to action. IGF-1R plays a role in the proliferation of cells, sending a signal for growth, differentiation, proliferation, and protection against apoptosis. “The observation is quite remarkable and very unexpected,” says Dr. Baserga, who has pioneered much of the basic science known about IGF-1R’s role in cancer development and as a potential anticancer drug target for pharmaceutical companies. “It’s a one-two punch. We knew that targeting the IGF receptor induces apoptosis, but unexpectedly, it also induced a host immune response that strengthens the killing of tumor cells.”

The study results appear April 15 in the Journal of Clinical Oncology. “This treatment has the potential to eventually be used for other cancers,” Dr. Andrews says.

But not yet. Despite the promising results, the work, for now, is on hold. The Food and Drug Administration has required more preclinical data. In addition, the scientists are frustrated by the lack of available antisense, which must be produced according to strict FDA standards. In the study, Dr. Andrews removed each patient’s tumor, made a suspension of tumor cells, and then treated them outside the body with antisense to IGF-1R. He then implanted the treated cells, now encapsulated in special “diffusion” chambers, in the patient’s abdomen for 24 hours, allowing the antisense to kill tumor cells through apoptosis.

It’s unclear exactly how the host response works. “We think that when the cells die, they release factors, perhaps small peptides, that are directly cytotoxic to the tumor and at the same time, may be immunogenic,” says Dr. Andrews. “We have evidence that over time, a T-cell cellular immune response may be generated.” “It’s not totally immunological,” says Dr. Aiken. “We know that there is an immediate programmed cell death reaction in the chambers. When we put the chamber in the abdomen, the treated cells are somehow transported to the brain and the glioblastoma. It has a specific effect, yet it’s not given at the tumor site.” Some patients had treatable side effects such as deep vein thrombosis.

Antisense therapy is designed to target and to turn off the mutated genes that cause cancer. Antisense DNA drugs work by binding to RNA messages from disease genes so that the genetic code in the RNA cannot be read. In contrast to the shotgun approach of chemotherapy, which kills both normal and cancerous cells, antisense exclusively attacks cancer cells. When the gene translation mechanism is turned off, cells can no longer make the protein products that cause disease.

If the trial for this therapy eventually re-opens, the researchers may continue the IGF-1R antisense strategy as a treatment after traditional therapies fail. They hope to also open new trials in which the IGF-1R antisense is given as an initial treatment at diagnosis.

The technology has been tested on laboratory rats, both with intact immune systems and on those that lack immune systems, with positive results, the researchers say. The technology can be applied to other cancers, such as prostate, breast, lung and melanoma. None has gone to clinical trials for those cancers as yet, however.

“The only way to make headway against this deadly disease is try a new paradigm,”

Dr. Aiken says. “It’s one thing to treat rat tumors, but another to treat very sick people. We not only want to improve the patient’s quality of life, we want to effect a cure.”


Story Source:

The above story is based on materials provided by Jefferson Medical College. Note: Materials may be edited for content and length.


Cite This Page:

Jefferson Medical College. "Antisense Treatment Promising For Deadly Brain Tumors." ScienceDaily. ScienceDaily, 17 April 2001. <www.sciencedaily.com/releases/2001/04/010417074841.htm>.
Jefferson Medical College. (2001, April 17). Antisense Treatment Promising For Deadly Brain Tumors. ScienceDaily. Retrieved August 31, 2014 from www.sciencedaily.com/releases/2001/04/010417074841.htm
Jefferson Medical College. "Antisense Treatment Promising For Deadly Brain Tumors." ScienceDaily. www.sciencedaily.com/releases/2001/04/010417074841.htm (accessed August 31, 2014).

Share This




More Health & Medicine News

Sunday, August 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

We've Got Mites Living In Our Faces And So Do You

We've Got Mites Living In Our Faces And So Do You

Newsy (Aug. 30, 2014) A new study suggests 100 percent of adult humans (those over 18 years of age) have Demodex mites living in their faces. Video provided by Newsy
Powered by NewsLook.com
Liberia Continues Fight Against Ebola

Liberia Continues Fight Against Ebola

AFP (Aug. 30, 2014) Authorities in Liberia try to stem the spread of the Ebola epidemic by raising awareness and setting up sanitation units for people to wash their hands. Duration: 00:41 Video provided by AFP
Powered by NewsLook.com
California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

California Passes 'yes-Means-Yes' Campus Sexual Assault Bill

Reuters - US Online Video (Aug. 30, 2014) California lawmakers pass a bill requiring universities to adopt "affirmative consent" language in their definitions of consensual sex, part of a nationwide drive to curb sexual assault on campuses. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
3 Things To Know About The Ebola Outbreak's Progression

3 Things To Know About The Ebola Outbreak's Progression

Newsy (Aug. 29, 2014) Here are three things you need to know about the deadly Ebola outbreak's progression this week. 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