Ovarian Cancer Immunotherapy Using Redirected Endogenous Anti-Gal Antibody
Abstract
We proposed that decorating ovarian tumor cells with alpha-Gal (using RGD*-alpha-Gal) will lead to their destruction by patients' naturally occurring antibody against alpha-Gal. We demonstrated staining of alpha-Gal+ tumor cells with FITC-conjugated IB4 lectin, as well as with human serum and secondary antibody. We also developed an in vitro assay to measure complement-dependent cytotoxicity (CDC) of tumors expressing alpha-Gal. We showed in mice that human serum containing anti-alpha-Gal antibody induced regression of alpha-Gal -expressing L5178Y tumor. Then we tested if alpha-Gal- tumor cells that express alphaVBeta3 integrin will bind RGD*-alpha-Gal (via RGD*) to the alphaVBeta3 integrin to express sufficient alpha-Gal to allow their destruction by anti-Gal antibody and complement. Tumor cells expressing the alphaVBeta3 integrin were treated with RGD*-alpha-Gal, followed by direct staining with FITC-IB4 lectin or with anti-alpha-Gal antibody and tested for indirect detection with anti-Gal antibody or for CDC. While detection of alpha-Gal was seen at low levels in some experiments, we were not able to reproducibly show sufficient levels to enable translation into clinical treatment simulation in vitro or in mice. These results suggest that we should be pursuing means to further increase the alpha-Gal expression we can induce on these tumors prior to trying to proceed to model treatment strategies in vitro or in vivo. Novel approaches towards this goal have been proposed and are detailed in the "linked" annual report being submitted by our co-investigator, Dr. Laura Kiessling.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2009
- Accession Number
- ADA519460
Entities
People
- Paul M Sondel
Organizations
- University of Wisconsin–Madison