Infectious disease researchers develop basis for experimental melanoma treatment

While investigating a fungus known to cause an infection in people with AIDS, two grantees of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), unexpectedly discovered a potential strategy for treating metastatic melanoma, one of the deadliest forms of skin cancer. The treatment approach, which involves combining an antibody with radiation, has since been further developed and is expected to enter early-stage human clinical studies in 2007.

"This is an excellent example of how scientific research in one discipline may have payoffs in a completely unpredictable way," says NIAID Director Anthony S. Fauci, M.D. "This important AIDS-related research has led to the development of a promising therapeutic strategy for a terrible cancer that affects thousands of people each year."

Arturo Casadevall, M.D., Ph.D., of the Albert Einstein College of Medicine at Yeshiva University, in New York City, and his research team began studying the biology of the skin pigment melanin to better understand why its synthesis plays a role in the process whereby certain yeast-like fungi, specifically Cryptococcus neoformans, cause disease in some people. C. neoformans can cause cryptococcosis, a potentially fatal fungal infection that can lead to inflammation of the brain and death in people with AIDS and other immunocompromised individuals.

The researchers created an infection-fighting antibody, known as a monoclonal antibody, that binds to melanin based on scientific evidence suggesting that when melanin is synthesized, it causes the immune system to react in a way that might create antibodies to fend off C. neoformans infection. Based on this finding, Dr. Casadevall theorized that melanomas might contain melanin that would allow the monoclonal antibody to deliver radiation to tumor cells. Dr. Casadevall then teamed with his colleague Ekaterina Dadachova, Ph.D., an expert in nuclear medicine and fellow NIAID grantee, to investigate whether the melanin-binding antibody could be converted into an anti-tumor drug.

In a study published in October 2004, Dr. Casadevall and Dr. Dadachova, the study's lead author, combined the C. neoformans monoclonal antibodies with radiation to create radiolabeled antibodies. They then tested these radiolabeled antibodies in mice to determine their effectiveness in attacking melanoma tumors. Initially, the mice had melanoma tumors ranging from 0.6 to 1.0 centimeters (cm) in diameter. After receiving a single dose of the radiolabeled antibodies, tumor growth was completely inhibited and near total tumor regression occurred in those animals with smaller tumors (0.6 to 0.7 cm in diameter). Further, the treated mice showed no signs of kidney or other organ damage and none died during the 30-day study. Conversely, tumors continued to aggressively grow in the untreated control group and by day 20, all but one of the eight untreated mice had died.

In November 2006, Pain Therapeutics, Inc., a San Francisco-based biopharmaceutical company, licensed the radiolabeled monoclonal antibody technology from the Albert Einstein College of Medicine. The company intends to begin testing it as a metastatic melanoma treatment in small human clinical trials in 2007. According to the American Cancer Society, melanoma accounts for approximately five percent of all skin cancers but causes roughly 75 percent of all skin cancer-related deaths.

Dr. Casadevall credits his promising discovery to luck and a hunch that paid off. "Scientific breakthroughs often occur completely through serendipity, and this is just one of those instances," says Dr. Casadevall. "We're still working on cryptococcosis and developing a general strategy for using radiolabeled monoclonal antibodies to fight infectious diseases."

His laboratory continues to examine the underlying causes of cryptococcosis, and in continued collaboration with Dr. Dadachova, is exploring the use of radiolabeled monoclonal antibodies to treat infectious diseases.

Source: NIH/National Institute of Allergy and Infectious Diseases

Related stories:

Scientists treat cancer as an infectious disease -- with promising results
Researchers at the Albert Einstein College of Medicine of Yeshiva University have shown for the first time that cancers can be successfully treated by targeting the viruses that cause them. The findings, published in the October 31 issue of PloS One, also raise the possibility of preventing cancer by destroying virus-infected cells before they turn cancerous.
1918 flu antibodies resurrected from elderly survivors
Ninety years after the sweeping destruction of the 1918 flu pandemic, researchers at Monroe Carell Jr. Children's Hospital at Vanderbilt have recovered antibodies to the virus – from elderly survivors of the original outbreak.
New protocol streamlines therapy that makes more kidney transplants possible
A new therapy developed at Cedars-Sinai Medical Center improves transplant rates and outcomes for patients awaiting living- and deceased-donor kidney transplantation, according to a study published in the July 17 issue of the New England Journal of Medicine.
Nanotechnology, biomolecules and light unite to 'cook' cancer cells
Researchers are testing a new way to kill cancer cells selectively by attaching cancer-seeking antibodies to tiny carbon tubes that heat up when exposed to near-infrared light.
OHSU discovery may lead to early cancer detection
This week researchers in the Oregon Health & Science University (OHSU) Oregon Stem Cell Center and the OHSU Digestive Health Center are shining a new ray of hope on patients with pancreatic cancer. They’ve developed new reagents, or antibodies, that can recognize this often lethal disease. This important discovery may one day lead to earlier detection and treatment.
The most natural drug
In the fight against infection, the human immune system isn’t ready for a war. Vaccines push the immune system to create defenses against illness, but they take time to work. A new process developed by scientists at the Oklahoma Medical Research Foundation (OMRF) and Emory University stands to revolutionize the process.
Nanosize Rods Light Up Pancreatic Cancer Cells
Quantum dots have shown promise as ultrabright contrast agents for use in a variety of cancer imaging studies. Now, a team of investigators at the Multifunctional Nanoparticles in Diagnosis and Therapy of Pancreatic Cancer Platform Partnership, headed by Paras Prasad, Ph.D., of the State University of New York at Buffalo, has shown that quantum rods may perform even better than their spherical cousins.
Experimental drug shows promise in treating certain lymphomas
New clinical data showed some cancer patients with recurrent lymphoma benefited from an experimental drug called AME-133v, said a researcher at the University of Alabama at Birmingham (UAB).

News discussion:

Infectious Disease Researchers- in Medicine & Health news