Corporate Banner
Satellite Banner
Technology
Networks
Scientific Communities
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Weapon Fights Drug-Resistant Tumors

Published: Monday, February 03, 2014
Last Updated: Monday, February 03, 2014
Bookmark and Share
A new study from MIT reveals a way to combat recurrent tumors with a drug that makes them more vulnerable to the antibody treatment.

Cancer drugs that recruit antibodies from the body’s own immune system to help kill tumors have shown much promise in treating several types of cancer. However, after initial success, the tumors often return.

The drug, known as cyclophosphamide, is already approved by the U.S. Food and Drug Administration (FDA) to treat some cancers.

Antibody drugs work by marking tumor cells for destruction by the body’s immune system, but they have little effect on tumor cells that hide out in the bone marrow. Cyclophosphamide stimulates the immune response in bone marrow, eliminating the reservoir of cancer cells that can produce new tumors after treatment.

“We’re not talking about the development of a new drug, we’re talking about the altered use of an existing therapy,” says Michael Hemann, an assoc. prof. of biology, a member of MIT’s Koch Institute for Integrative Cancer Research and one of the senior authors of the study. “We can operate within the context of existing treatment regimens but hopefully achieve drastic improvement in the efficacy of those regimens.”

Jianzhu Chen, a prof. of immunology and a member of the Koch Institute, is also a senior author of the paper, which appears in Cell. The lead author is former Koch Institute postdoctoral researcher Christian Pallasch, now at the Univ. of Cologne in Germany.

Finding cancer’s hiding spots

Antibody-based cancer drugs are designed to bind to proteins found on the surfaces of tumor cells. Once the antibodies flag the tumor cells, immune cells called macrophages destroy them. While many antibody drugs have already been approved to treat human cancers, little is known about the best ways to deploy them, and what drugs might boost their effects, Hemann says.

Antibodies are very species-specific, so for this study, the researchers developed a strain of mice that can develop human lymphomas (cancers of white blood cells) by implanting them with human blood stem cells that are genetically programmed to become cancerous. Because these mice have a human version of cancer, they can be used to test drugs that target human tumor cells.

The researchers first studied an antibody drug called alemtuzumab, which is FDA-approved and in clinical trials for some forms of lymphoma. The drug successfully cleared most cancer cells, but some remained hidden in the bone marrow, which has previously been identified as a site of drug resistance in many types of cancer.

The study revealed that within the bone marrow, alemtuzumab successfully binds to tumor cells, but macrophages do not attack the cells due to the presence of lipid compounds called prostaglandins, which repress macrophage activity. Scientists believe the bone marrow naturally produces prostaglandins to help protect the immune cells that are maturing there. Tumor cells that reach the bone marrow can exploit this protective environment to aid their own survival.

Tricking the immune system

The MIT team then tested a variety of cancer drugs in combination with alemtuzumab and discovered that cyclophosphamide can rewire the bone marrow microenvironment to make it much more receptive to macrophages, allowing them to destroy the tumor cells hiding there.

“After you treat with cyclophosphamide you get this flux of macrophages into the bone marrow, and these macrophages are now active and very capable of consuming the targeted tumor cells,” Hemann says. “Essentially we are tricking the immune system to suddenly recognize an entity that it wouldn’t typically recognize and aggressively go after antibody-bound tumor cells.”

Following treatment with this combination of drugs, the mice survived, tumor-free, for the duration of the study—about 18 months.

Cyclophosphamide is often given to cancer patients as part of frontline chemotherapy. However, the MIT team found that when given in combination with alemtuzumab, it was effective at much lower doses than are typically given, which could help reduce side effects.

They also found that the timing of the drug delivery was critical: The antibody drug and cyclophosphamide have to be given at the same time, so that cyclophosphamide can create the right type of environment for macrophages to become activated in the bone marrow.

The researchers also got good results by combining cyclophosphamide with another antibody drug, rituximab, which is used to treat lymphoma and leukemia. They now plan to test cyclophosphamide with other types of antibody drugs, including those that target breast and prostate tumors. Both of those cancers often metastasize to the bone marrow and are very difficult to treat once they spread.

Pallasch is also planning to begin testing the alemtuzumab-cyclophosphamide combination in lymphoma patients.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,500+ scientific posters on ePosters
  • More Than 3,800+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Intensity of Desert Storms May Affect Ocean Phytoplankton
MIT study finds phytoplankton are extremely sensitive to changing levels of desert dust.
Tuesday, September 01, 2015
Searching Big Data Faster
Theoretical analysis could expand applications of accelerated searching in biology, other fields.
Thursday, August 27, 2015
Protein Found to Play a Key Role in Blocking Pathogen Survival
Calprotectin fends off microbial invaders by limiting access to iron, an important nutrient.
Wednesday, August 26, 2015
A Metabolic Master Switch Underlying Human Obesity
Researchers find pathway that controls metabolism by prompting fat cells to store or burn fat.
Friday, August 21, 2015
Capturing Cell Growth in 3-D
Spinout’s microfluidics device better models how cancer and other cells interact in the body.
Monday, August 17, 2015
Better Estimates of Worldwide Mercury Pollution
New findings show Asia produces twice as much mercury emissions as previously thought.
Thursday, August 13, 2015
Real-Time Data for Cancer Therapy
Biochemical sensor implanted at initial biopsy could allow doctors to better monitor and adjust cancer treatments.
Thursday, August 06, 2015
Identifying a Key Growth Factor in Cell Proliferation
Researchers discover that aspartate is a limiter of cell proliferation.
Friday, July 31, 2015
Firms “Under-invest” in Long-Term Cancer Research
Tweaks to the R&D pipeline could create new drugs and greater social benefit.
Thursday, July 30, 2015
Nanoparticles Can Clean Up Environmental Pollutants
Researchers have found that nanomaterials and UV light can “trap” chemicals for easy removal from soil and water.
Thursday, July 23, 2015
Bacterial Computing
The “friendly” bacteria inside our digestive systems are being given an upgrade, which may one day allow them to be programmed to detect and ultimately treat diseases such as colon cancer and immune disorders.
Monday, July 13, 2015
Researchers Develop Genetic Tools to Engineer Common Gut Bacterium
Researchers from the Massachusetts Institute of Technology have developed genetic parts that can be combined to program the commensal gut bacterium Bacteroides thetaiotaomicron.
Friday, July 10, 2015
Chemists Design a Quantum-Dot Spectrometer
New instrument is small enough to function within a smartphone, enabling portable light analysis.
Friday, July 03, 2015
Longstanding Problem Put to Rest
Proof that a 40-year-old algorithm for comparing genomes is the best possible will come as a relief to computer scientists.
Thursday, June 11, 2015
Tough biogel structures produced by 3-D printing
Researchers have developed a new way of making tough — but soft and wet — bio-compatible materials, called “hydrogels,” into complex and intricately patterned shapes.
Wednesday, June 03, 2015
Scientific News
Health Risks of Saturated Fats Aggravated by Immune Response
Research shows that the presence of saturated fats resulted in monocytes migrating into the tissues of vital organs.
Changing the Biological Data Visualisation World
Scientists at TGAC, alongside European partners, have created a cutting-edge, open source community for the life sciences.
NIH Study Finds Calorie Restriction Lowers Some Risk Factors for Age-Related Diseases
Two-year trial did not produce expected metabolic changes, but influenced other life span markers.
Immunotherapy Agent Benefits Patients with Drug-Resistant Multiple Myeloma in First Human Trial
Daratumumab proved generally safe in patients, even at the highest doses.
Low-level Arsenic Exposure Before Birth Associated with Early Puberty in Female Mice
Study examine whether low-dose arsenic exposure could have similar health outcomes in humans.
Inciting an Immune Attack On Cancer Cells
A new minimally invasive vaccine that combines cancer cells and immune-enhancing factors could be used clinically to launch a destructive attack on tumors.
‘Mutation-Tracking’ Blood Test for Breast Cancer
Scientists have developed a blood test for breast cancer able to identify which patients will suffer a relapse after treatment, months before tumours are visible on hospital scans.
Cellular Contamination Pathway for Heavy Elements Identified
Berkeley Lab scientists find that an iron-binding protein can transport actinides into cells.
Intensity of Desert Storms May Affect Ocean Phytoplankton
MIT study finds phytoplankton are extremely sensitive to changing levels of desert dust.
Common ‘Heart Attack’ Blood Test May Predict Future Hypertension
Small rises in troponin levels may have value as markers for subclinical heart damage and high blood pressure.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!