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Penn Researchers Developing Protein ‘Passport’ To Help Deliver Cancer Drugs

Mesothelioma Applied Research

The body’s immune system is designed to defend against bacteria, viruses and other perceived “foreign invaders” that assault the body. Unfortunately, the immune system doesn’t distinguish between harmful bacteria and friendly foreign objects such as medical devices implanted in a patient or nanoparticles used to deliver medicine to tumors. That poses complications to doctors trying to administer treatments to people with cancer, including malignant mesothelioma, a cancer caused by exposure to asbestos.

Doctors would like to avoid triggering an inflammatory response in cancer patients when they administer medicine or when implanting a pacemaker or artificial joint. Researchers at the University of Pennsylvania are experimenting with what they describe as “a passport” to allow therapeutic devices to get past the immune system, according to new research published in the journal Science.

The human body’s innate immune system responds to foreign bodies in a generalized way, trying to destroy anything it doesn’t recognize as a part of the body. The team of Penn researchers says the solution is to make the foreign particles seem like part of the body so the immune system doesn’t destroy them.

The researchers reported this week that they had accomplished that feat in lab mice, attaching customized protein fragments to foreign particles that tricked the animals’ immune system. The key was tricking the immune-system “border guards” known as macrophages that are a type of white blood cell that find and eat invaders. Macrophages continually monitor the bloodstream for a type of protein called CD47, a marker of self. If an object such as a red blood cell has CD47 on its membrane, the macrophages let it pass.

The Penn team leader, Dennis E. Discher, a professor of chemical and biomolecular engineering, compared CD47 to a passport that identifies a cell as part of the body rather than a foreign object. The research team attached fragments of CD47 to plastic nanoparticles, then injected them into laboratory mice. Nanoparticles, which are smaller than one-billionth of a meter, are useful in delivering, antibodies, drugs and imaging agents and are being studied for diagnosis and treatment of cancer, according to the National Cancer Institute.

The researchers said the technique enhanced the performance of nanoparticles carrying tumor-shrinking medicine and other loaded with dye to capture images of the tumors. They observed that the particles carrying a cancer drug Taxol were shrinking tumors in mice.

Discher said in an article in the Philadelphia Inquirer that the technique could be useful in overcoming resistance to much larger foreign objects in the body such as pacemakers and joint replacements.

Researchers not involved in the research called it a promising advance, though it will take some years before the technique is ready to use with human cancer patients.

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