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New study expands potential targets for cancer-fighting antibodies

A pre-clinical study that combines chemotherapy and immunotherapy shows that antibodies, which have been successful in treating certain cancers, can enhance the immune system’s ability to track down and kill cancer cells.


The research, funded by the Cancer Research Institute and published in Cancer Research, could lead to new therapies that target markers on the surface of cancer cells.


While antibody treatments like Herceptin, which targets proteins associated with breast cancer, and Rituxan, a therapy for B cell lymphoma, represent major breakthroughs in cancer treatment, most markers that can distinguish cancer cells from normal cells are found inside cancer cells, where antibodies may not be able to reach them.


Gerd Ritter, associate director of the New York Branch of the Ludwig Institute for Cancer Research and a leading member of the Cancer Vaccine Collaborative, said the new study shows that antibodies which reach intracellular targets can delay tumor growth and prolong survival in patients when combined with chemotherapy.


"Therapies that can successfully target cancer antigens found within cancer cells may be able to fight cancer without causing unwanted side effects due to collateral damage to healthy cells," Ritter said.


According to the Cancer Research Institute, the study could lead to clinical trials that “would bridge what immunologists refer to as passive immunotherapy and active immunotherapy.”


Immunotherapy alters the body’s natural reaction to disease. A healthy immune system will not attack cells, even cancer cells, that it does not recognize as foreign. Immunotherapy tricks the immune system into recognizing cancer cells as foreign substances, triggering an attack on those cells.


Active immunotherapy treatments, such as vaccines that stimulate the immune system to fight disease, are made with the patient’s own cells in the lab, then injected back into the body.


Passive immunotherapy treatments are created with so-called monoclonal antibodies that are designed to identify specific antigens on the cancer cells. If successful, the immune system will recognize the monoclonal antibodies and destroy the cancer cells. Herceptin and Rituxan are commonly used monoclonal antibody therapies.


"It's passive because we're using antibodies manufactured outside the body—the body doesn't have to do the work to make these antibodies,” Ritter said. “It's a powerful strategy that for the first time capitalizes on the full therapeutic potential of antibodies as mediators of tumor elimination.”


In the current study, researchers tested an antibody against the cancer antigen NY-ESO-1 in a model of colon cancer. The antibody alone had no effect, but by using chemotherapy to release the antigen prior to delivering the antibody, they significantly delayed cancer progression and prolonged survival. The researchers got similar results in a test on another cancer model, suggesting that the approach could be used in combination with various chemotherapies for different types of tumors.


"The study provides proof-of-principle for a powerful new strategy that may greatly expand the arsenal of potential targets for cancer drug development and that could be broadly applicable to many different cancer types," said Hiroyoshi Nishikawa, associate professor in the Department of Experimental Immunology at the Immunology Frontier Research Center, Osaka University, and a senior author on the paper.


Pleural mesothelioma, a cancer of the lining of the lung and abdomen caused by asbestos exposure, has proven resistant to chemotherapy alone. The average prognosis for patients is typically no more than a year or two.