New Approach in the Analysis of Immune Responses to Cancer 

Tumor-specific antibodies in the blood might be another step in early cancer detection. Antibodies, the weapons used by the body’s own immune system to fight pathogens, have been employed in clinical practice and in the laboratory for many years. They can be used, for example, to diagnose viral infections such as the so-called swine flu and also to treat cancer with antibodies such as Herceptin and Erbitux. They also play an important role in research, such as to show that a patient’s own immune system reacts to cancer cells and, thus, to prove that the immune system does interact with cancer cells. Due to this fact it is possible today to attempt prevention of cancer using vaccines and to treat existing cancers by specific boosting of the immune response.

Professor Dr. Dirk Jäger of the National Center for Tumor Diseases (NCT) Heidelberg, jointly with Dr. Lloyd J. Old of the Ludwig Institute for Cancer Research (LICR) in New York City, has been systematically studying antibody responses in cancer patients. In the latest issue of the Proceedings of the National Academy of Sciences (PNAS) they have now published results that might lead to new approaches in the early detection of ovarian and pancreatic cancers. In addition, these research results might help to identify eligible patients for targeted cancer therapies. 

The researchers investigated patient serum to detect antibody responses to more than 8,000 proteins using what are called protein microarrays. These are collections of capture proteins arranged in so-called spots in a very small space. They studied blood of healthy persons and of patients suffering from ovarian and pancreatic cancers. This detection method allows subsequent discrimination between spots with or without interaction. The investigators found significantly more antibodies in the blood of ovarian cancer patients than in the blood of pancreatic cancer patients. "This might be a reason for the poor prognosis of pancreatic cancer, " Dirk Jäger speculates. "The fewer antibodies are present in a patient’s blood, the poorer his or her immune system seems to recognize and to reject the cancer."

A patient’s antibody response to a tumor offers even further possibilities: Thus, detection of antibodies in the blood might be used for detecting cancer at an early stage. This would be particularly important in the case of pancreatic and ovarian cancers, as Dirk Jäger emphasizes: "These types of cancer are usually not detected until the tumor has reached a very advanced stage. This is very unfavorable for the prognosis. If we were able to detect the tumors earlier, the chances of cure for the patients would be much better," said cancer specialist Jäger.

The ambitious ‘cancer seromics’ project is just at the beginning of a series of much more comprehensive analyses. The research results obtained in this project, i.e., which antibody reacts with which protein in a tumor, will be fed into a database that will be made accessible for cancer researchers around the globe. The aim is to find significant markers for early detection as soon as possible, to develop vaccine therapies for specific cancers and to explore new immune therapy approaches in cancer treatment. "The immune system as a weapon against cancer has a lot more to offer," says Jäger. "It is time to make more use of this opportunity in the battle against the treacherous disease of cancer."

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. 2010 Mar 16;107(11):5088-93.
DOI: 10.1073/pnas.0914213107
 
The National Center for Tumor Diseases (NCT) Heidelberg is a joint project of the German Cancer Research Center (DKFZ), Heidelberg University Hospitals, Thorax Clinic Heidelberg and the German Cancer Aid (Deutsche Krebshilfe). The goal of the NCT is to link promising approaches from cancer research with patient care from diagnosis over treatment to follow-up care and prevention. At the heart of NCT is the interdisciplinary Tumor Outpatient Clinic where patients benefit from an individual treatment plan provided in a timely manner by interdisciplinary expert boards called Tumor Boards. Participation in clinical trials provides access to innovative therapies. Thus, NCT is a trend-setting platform for the transfer of new research results from the laboratory to clinical practice.

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