Abstract 797: Characterization of endogenous antibodies to tumor
Authors: Rich Barrie S. , Williams Andrew R. , Honeyman Joshua N. , Smith Peter T. , Simon Sanford M. 
Published: June 2012

Early detection of malignancy is crucial for long-term survival in patients with various types of cancer; however, this remains a challenge in a wide variety of tumors. This study tests whether a patient's own antibodies can be used diagnostically for early detection.

It has been proposed that the body is undergoing continuous surveillance by the immune system, with elimination of newly transformed cells. Cancer becomes a clinical problem when the immune system fails to eliminate these cells. Many studies have looked at the immune system, particularly antibodies, as a therapeutic tool against tumor-associated antigens. However, single antigens are rarely sensitive or specific for a certain tumor type. The use of panels of antigens and antibodies has increased the sensitivity of tumor detection, however not sufficiently. We tested if the polyclonal spectra of antibodies that an individual creates can still detect tumors even if the immune system cannot eliminate the tumor. These antibodies will vary considerably in affinity and specificity. The goal was to determine if they could serve as a dependable and reliable means to detect microscopic foci of tumor, and distinguish transformed from normal tissue. We therefore tested for the presence of endogenous antibodies in tissue from multiple mouse models of cancer, including models consisting of over expression of an oncogene in addition to deletion of a tumor suppressor gene.

We obtained tissue from four mouse models of tumor: liver tissue from transgenic alb-myc mice, breast tissue from transgenic MMTV-neu mice, and prostate tissue from two prostate models (a transgenic Pb-myc model and a knock-out PTEN model). These were compared to matched tissue samples from wild-type mice. Paraffin embedded and frozen section slides of test and matched wild-type tissue were tested for the presence of endogenous antibody with immunofluorescence, using a rabbit secondary anti-mouse IgG. Immunofluorescence with a goat anti-rabbit IgG served as a negative control.

There was a significantly higher intensity of immunofluorescence in tissue from mice genetically engineered to have tumors compared to the wild-type mice. Adjacent sections stained with H&E were evaluated by a veterinary histo-pathologist in a double-blind study. Areas marked as altered by H&E were significantly enhanced in antibody binding. Similar results were observed in the liver, prostate and breast cancer models. No signal was observed with the goat anti-rabbit negative control.

The results indicate that the spectra of endogenous antibodies have the potential to detect these genetically engineered tumors at early stages of transformation. The success of this approach opens the possibility of using these antibodies both diagnostically and therapeutically.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 797. doi:10.1158/1538-7445.AM2011-797