New Dimensions in the Analysis of the Immune Response to Cancer

Newswise — Cancer researchers have taken a major step forward toward what is planned to be the most comprehensive analysis of the body’s antibody response to human cancer, an enterprise that has been termed “cancer seromics.”

A leading laboratory in this field of antibodies and cancer is directed by Dr. Lloyd J. Old, of the Ludwig Institute for Cancer Research (LICR), who has been at the forefront of major advances in understanding the relation between immunity and cancer and in the development of immunotherapeutic approaches to cancer.

In a paper published in the Proceedings of the National Academy of Sciences (PNAS) this week, Dr. Sacha Gnjatic, Dr. Old and their colleagues at the LICR New York Branch of Human Cancer Immunology at Memorial Sloan-Kettering Cancer Center, Roswell Park Cancer Center, and the University of Heidelberg, report the successful application of a new microarray technology that has enabled the rapid and simultaneous screening of thousands of auto-reactive antibodies found in cancer patients. The technology could provide cancer immunologists with a significantly larger number of potential targets for cancer immunotherapy, as well as provide new diagnostic and prognostic tests for cancer.

Antibodies, the disease-fighting molecules produced by the immune system, have a long history of use in the laboratory and clinic, from diagnostic applications such as the detection of viral infections or prostate cancer, to the treatment of human cancer with antibodies such as Herceptin and Erbitux. They have also been critical in studying the body’s reaction to cancer and proving that the human immune system recognizes cancer cells as foreign, helping to resolve the century-long controversy about the role of immunity in cancer and providing a strong theoretical basis for the potential of cancer vaccines as a new approach to cancer therapy.

This massive effort to identify and validate the complete library of antigenic targets for cancer immunotherapy is made possible by the availability of arrays containing more than 8,000 different human proteins on a glass chip. Two human cancers were selected for the initial analysis – ovarian cancer and pancreas cancer. Because these cancers are usually found at a late, incurable stage, there is a great need to develop early detection systems and antibody responses to the emerging tumor could serve this purpose.

Sera from patients with ovarian cancer and pancreas cancer were used to screen the protein arrays and a large number of antibodies with reactivity to individual proteins were identified and ranked in terms of frequency and strength. As the analysis of the full range of human cancers progresses, a public database of the human antibodies response to human cancer will be constructed and available for investigators around the world to use and compare results.

As reported in the PNAS paper, ovarian cancer appears to induce a much broader antibody response than pancreas cancer, an observation that may shed light on the poor prognosis and response to therapy of pancreas cancer. Most important, the findings identify a range of cancer targets that can be the basis for new cancer diagnostic and screening tests, and for the development of cancer vaccines and other immunotherapeutic approaches to cancer.

Support for this project was provided to Dr. Gnjatic through a Coordinated Cancer Initiatives grant from the Cancer Research Institute, a nonprofit organization dedicated to harnessing the power of the immune system to treat, control, and prevent cancer.

Reference Publication: Gnjatic S, Ritter, E, Büchler MW, Giese NA, Brors B, Frei C, Murray A, Halama N, Chen Y-T, Andrews C, Ritter G, Old LJ, Odunsi K, and Jäger D. Seromic profiling of ovarian and pancreatic cancer. Proc Natl Acad Sci USA. Available on-line early edition March 1, 2010.

About the Ludwig Institute for Cancer Research (LICR) New York Branch of Human Cancer Immunology at Memorial Sloan-Kettering Cancer Center (MSKCC)

The New York Branch of Human Cancer Immunology at Memorial Sloan-Kettering Cancer Center is one of the ten research branches of the Ludwig Institute for Cancer Research, a global non-profit institute committed to improving the understanding and control of cancer through integrated laboratory and clinical discovery.

The New York Branch of Human Cancer Immunology’s main objective is the identification of suitable targets for antibody-based and vaccine-based immunotherapies of cancer. Over the years, the laboratory has defined a wide range of antibodies that target cell surface antigens on human cancer cells, as well as a range of intracellular antigens targeted by humoral and cellular immune responses. Based on detailed serological, biochemical, cellular, immunohistochemical and genetic characterization, a number of these antibodies and tumor antigens have been selected for early phase clinical trials. http://www.licr.org

About the Cancer Research Institute

The Cancer Research Institute (CRI) is the world’s only non-profit organization dedicated exclusively to the support and coordination of scientific and clinical efforts that will lead to the immunological treatment, control, and prevention of cancer. Guided by a world-renowned Scientific Advisory Council that includes four Nobel Prize winners and twenty-nine members of the National Academy of Sciences, CRI supports leading-edge cancer research at top medical centers and universities throughout the world. The Cancer Research Institute is ushering in a new era of scientific progress, hastening the discovery of effective cancer vaccines and other immune-based therapies that are providing new hope to cancer patients.

The Cancer Research Institute has one of the lowest overhead expense ratios among non-profit organizations, with more than 85 percent of its resources going directly to the support of its science, medical, and research programs. CRI meets or exceeds all 20 standards of the Better Business Bureau Wise Giving Alliance, the most comprehensive U.S. charity evaluation service, and according to Charity Navigator exceeds or meets industry standards and performs as well as or better than most cancer charities. CRI has also received an 'A' grade for fiscal disclosure and efficiency from the American Institute of Philanthropy as well as top accolades from other charity watchdog organizations. http://www.cancerresearch.org.