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

Join For Free

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 3,200+ scientific posters on ePosters
  • More Than 4,600+ 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

New System for Detecting Explosives
Spectroscopic system with chip-scale lasers cuts detection time from minutes to microseconds.
Wednesday, June 01, 2016
Illuminating Hidden Gene Regulators
New super-resolution technique visualizes important role of short-lived enzyme clusters.
Friday, May 27, 2016
Controlling RNA in Living Cells
Modular, programmable proteins can be used to track or manipulate gene expression.
Wednesday, April 27, 2016
Long-Term Drug Release
New tablet attaches to the lining of the GI tract, resists being pulled away.
Thursday, April 07, 2016
Pharmacy on Demand
New, portable system can be configured to produce different drugs.
Monday, April 04, 2016
A Programming Language for Living Cells
New language lets researchers design novel biological circuits.
Monday, April 04, 2016
Why Some Tumors Withstand Treatment
Mechanism uncovered that allows cancer cells to evade targeted therapies.
Thursday, March 17, 2016
Cancer Cells Remodel Environments Before Spreading
Researchers at MIT have found that the cancer cells remodel their environment to make it easier to reach nearby blood vessels.
Wednesday, March 16, 2016
Paving the Way for Metastasis
Cancer cells remodel their environment to make it easier to reach nearby blood vessels.
Tuesday, March 15, 2016
A New Way to Discover DNA Modifications
Researchers systematically find molecules that help regulate and protect DNA.
Wednesday, March 02, 2016
MIT Study: Carbon Tax Needed to Cut Fossil Fuel Consumption
Researchers at MIT have suggested that the technology-driven cost reductions in fossil fuels will lead the world to continue using all the oil, gas, and coal, unless governments pass new taxes on carbon emissions.
Thursday, February 25, 2016
Mapping Regulatory Elements
Systematically searching DNA for regulatory elements indicates limits of previous thinking
Wednesday, February 03, 2016
Curing Disease by Repairing Faulty Genes
New delivery method boosts efficiency of CRISPR genome-editing system.
Wednesday, February 03, 2016
Living a “Mixotrophic” Lifestyle
Some tiny plankton may have big effect on ocean’s carbon storage.
Tuesday, February 02, 2016
Faster Drug Discovery?
Startup develops more cost-effective test for assessing how cells respond to chemicals.
Friday, January 29, 2016
Scientific News
Platelets are the Pathfinders for Leukocyte Extravasation During Inflammation
Findings from the study could help in the prevention and treatment of inflammatory pathologies.
ASMS 2016: Targeting Mass Spectrometry Tools for the Masses
The expanding application range of MS in life sciences, food, energy, and health sciences research was highlighted at this year's ASMS meeting in San Antonio, Texas.
Benchtop Automation Trends
Gain a better understanding of current interest in and future deployment of benchtop automated systems.
Manufactured Stem Cells to Advance Clinical Research
Clinical-grade cell line will enable development of new therapies and accelerate early-stage clinical research.
Dengue Virus Exposure May Amplify Zika Infection
Researchers at Imperial College London have found that the previous exposure to the dengue virus may increase the potency of Zika infection.
Gender Determination in Forensic Investigations
This study investigated the effectiveness of lip print analysis as a tool in gender determination.
Identifying Novel Types of Forensic Markers in Degraded DNA
Scientists have tried to verify the nucleosome protection hypothesis by discovering STRs within nucleosome core regions, using whole genome sequencing.
Proteins in Blood of Heart Disease Patients May Predict Adverse Events
Nine-protein test shown superior to conventional assessments of risk.
Higher Frequency of Huntington's Disease Mutations Discovered
University of Aberdeen study shows that the gene change that causes Huntington's disease is much more common than previously thought.
Starving Stem Cells May Enable Scientists To Build Better Blood Vessels
Researchers from the University of Illinois at Chicago College of Medicine have uncovered how changes in metabolism of human embryonic stem cells help coax them to mature into specific cell types — and may improve their function in engineered organs or tissues.
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
3,200+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,600+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!