Developing Cancer Vaccines
A slew of new studies have recently been published involving one of the hottest topics of cancer research-cancer vaccines.
Traditional vaccines for infectious diseases such as measles, mumps and tetanus are effective because they expose the immune system to weakened versions of the disease. This exposure causes the immune system to respond by producing "antibodies" against the disease. Once the immune system has created specific antibodies, it can more readily destroy the disease the next time it invades the body.
With cancer, researchers are developing vaccines that may encourage the immune system to specifically recognize and attack cancer cells. These vaccines may then help the body reject tumors and prevent cancer from recurring.
In contrast to vaccines against infectious diseases, however, most cancer vaccines are currently being tested in patients after the disease is diagnosed, rather than before it develops, (although some promising preventive cancer vaccines are in the early stages of testing).
Without question, the development of vaccines against specific cancers represents one of the most promising avenues of cancer research today. Here is a sampler of some recent findings ...
A report just published in the Journal of Clinical Investigation has concluded that immunization with a so-called HER-2/neu "helper" may spur the response of antitumor T-cells in the body's immune system.
Dr. Keith Knutson and colleagues from the University of Washington in Seattle have developed a "HER-2/neu helper-peptide vaccine" that appears to elicit a strong anti-tumor response in breast and ovarian cancer patients.
They tested their vaccine in 18 patients whose tumors exhibited an abundance (overexpression) of the HER-2/neu protein on their cell surface. It is estimated that as many as a third of breast and ovarian cancers have such an overexpression.
Fourteen (83 percent) of the patients in the study demonstrated a marked response to the vaccine, measured in terms of reduction in tumor size and the number of anti-tumor antigens that were eventually produced.
Equally promising results have been achieved by researchers at Memorial Sloan-Kettering Cancer Center in New York. Writing in the journal Clinical Cancer Research, Dr. Paul Chapman and colleagues reported on a new vaccine-mixed ganglioside conjugate vaccine or MGV-that appears to induce anti-cancer antibodies against two different targets on a cancer cells.
MGV was designed to stimulate a patient's immune system to control or eradicate residual cancer cells after surgery, radiation or chemotherapy without damaging healthy tissue. Specifically, it stimulates the formation of antibodies to GM2 and GD2 gangliosides, which are present in many of the most common types of cancer.
The Sloan-Kettering study involved 31 patients with malignant melanoma or sarcoma. The vaccine induced antibodies to GM2 in 97 percent of the patients, and GD2 in 91 percent of the patients.
"This two-pronged attack may significantly enhance the efficacy of the vaccine against a variety of important cancers," the researchers wrote.
Another study has found that using smaller protein molecules to transport vaccines could give vaccines the ability to "super-stimulate" antibodies against a number of cancers and infectious diseases.
The research, published in the Journal of Immunology, demonstrated that combining a group of small PADRE proteins with anti-cancer antigens produces a significantly higher immune response than when larger protein molecules are used.
The proteins that are currently included in vaccines are bulky and complex, typically composed of multiple carbohydrate molecules attached to a single large protein carrier molecule. The PADRE molecule, on the other hand, is comparatively much smaller and attaches to a single carbohydrate molecule.
This smaller, simpler vaccine makes it easier to manufacture synthetically. Also, because the PADRE molecule is so small, it does not attract as much of an "anti-protein response" from the body's normal infection fighting cells, which can render traditional vaccines ineffective.
Finally, because PADRE is manufactured synthetically and not derived from an infectious organism like other vaccines, it has the potential to cause fewer adverse side effects-an extremely important benefit that has been demonstrated in early clinical trials.
SOURCES:
Journal of Clinical Investigation, February 2001; 107:477-484
Clinical Cancer Research, December 2000; 6:4658-4662
Journal of Immunology, 2000; 164:1625-1633
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