Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers unveil strategy for creating actively-programmed anti-cancer molecules

12.07.2006
Novel approach could substantially improve a range of anti-cancer therapy

The new study, which was published July 5 in an advanced, online edition of the Proceedings of the National Academy of Sciences, achieved a significant enhancement of the treatment of metastatic breast cancer in animal models. The study showed the new hybrid compound remained in circulation for a week. In comparison, the small molecule drug was cleared in a matter of minutes.

"Although the study focused specifically on breast cancer, these new findings could have broad application in the treatment of a number of other cancers, potentially increasing the efficacy of a number of existing or undeveloped small molecule therapies," said Subhash C. Sinha, Ph.D., associate professor in the Scripps Research Department of Molecular Biology and the Skaggs Institute for Chemical Biology, who led the research with Scripps Research President Richard A. Lerner, M.D., Lita Annenberg Hazen Professor of Immunochemistry, Cecil H. and Ida M. Green Chair in Chemistry, and a member of the Skaggs Institute for Chemical Biology.

In the study, the scientists created what is known as a "chemically programmed antibody" by using small cell-targeting molecules and a non-targeting catalytic monoclonal aldolase antibody in a novel self-assembly strategy. Antibodies are proteins produced by immune cells that are designed to recognize foreign pathogens harmful to the body; monoclonal antibodies are produced in the laboratory from a single cloned B-cell, the immune system cell that makes antibodies.

"By bringing together chemistry and biology, our approach provides a way to break the traditional one antibody-one target axiom of immunochemistry," said Lerner. "This new hybrid technology offers great possibilities for the enhanced treatment and diagnosis of a variety of diseases, including cancer."

Preventing Breast Cancer Metastasis

In the study, the researchers used the unique assembly strategy to create a novel compound to combat metastatic breast cancer.

Breast cancer can be a treatable disease, but only if diagnosed early. Since the prognosis grows considerably worse once the cancer has spread to other organs, the prevention of metastasis-the phenomenon in which cancer cells separate from a tumor mass, move through the bloodstream, anchor down in a distant tissue or organ to begin a new cancer-remains a critically important goal. The most recent figures from the Centers for Disease Control and Prevention indicate that more than 200,000 U.S. women are diagnosed with new cases of invasive breast cancer each year and that more than 40,000 of these women will die of the disease-usually the end result of metastasis.

The therapeutic use of monoclonal antibodies has expanded rapidly over the last several years precisely because of their long half-life, combined with their overall lack of toxicity and the fact that they can be easily designed and produced. For cancer treatment, the ability of antibodies to direct immune system responses to specific tumor types is one of the factors that have led to their increased use.

Until recently, it had been widely accepted that while antibodies possess a number of therapeutically advantageous traits, treatment with monoclonals required a different antibody for each specific target. However, the paper's authors have been showing that scientists can use different small molecule targeting agents-called programming agents or adapters-to selectively direct the same antibody to different sites for different uses so that only a single antibody is required for multiple tasks.

Recent research led by Scripps Research Professor Carlos F. Barbas III, for example, used the chemically programmed antibody approach in a melanoma model, dramatically enhancing the effectiveness of a small molecule drug (International Journal of Cancer 119 (5), 1194-1207, March 28, 2006).

In the new study, the researchers used a self-assembly process to link small synthetic molecules and a well-known catalytic monoclonal antibody, mAb38C2, through chemical bonding, a modification that resulted in the reprogramming of the specificity of the antibody to match the binding specificity of the small molecule. In this way, the antibodies were directed to the target avb3 integrin-a cell membrane protein expressed on a variety of cancers and the vasculatures they produce.

"Key to this unique approach is the ability of the small molecule targeting agents-called programming agents or adapters-to selectively react in the antibody binding sites without compromising the targeting property of the adapters," notes Sinha.

The results showed those mice treated with the new compound developed significantly fewer metastases than those treated with other similar compounds or the antibody alone. These results, the study noted, were a "significant enhancement in the therapeutic efficacy" of the integrin antagonist directly attributable to the chemically programmed antibody approach.

Moreover, the study indicated that this approach allows for the effective assembly of chemically programmed antibodies in vivo or in vitro, widening the possibilities for their therapeutic application. The compound could be created in vitro and delivered as a conventional single therapy. Alternately, the small molecule and antibody could be injected separately, with the new complex formed in vivo. The authors note that even though the administration of two separate compounds might complicate regulatory approval, the regimen could have advantages-for example, an imaging agent could be attached to the small molecule, allowing a physician to monitor localization of a drug before arming the agent with the antibody molecule.

Keith McKeown | EurekAlert!
Further information:
http://www.scripps.edu

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>