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Antibodies elicited by the first non-viral prophylactic cancer vaccine show tumor-specificity and immunotherapeutic potential

Title: Antibodies elicited by the first non-viral prophylactic cancer vaccine show tumor-specificity and immunotherapeutic potential.
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Name(s): Lohmueller, Jason J., author
Sato, Shuji, author
Popova, Lana, author
Chu, Isabel M., author
Tucker, Meghan A., author
Barberena, Roberto, author
Innocenti, Gregory M., author
Cudic, Mare, author
Ham, James D., author
Cheung, Wan Cheung, author
Polakiewicz, Roberto D., author
Finn, Olivera J., author
Type of Resource: text
Genre: Article
Date Issued: 2016-10-22
Summary: MUC1 is a shared tumor antigen expressed on >80% of human cancers. We completed the first prophylactic cancer vaccine clinical trial based on a non-viral antigen, MUC1, in healthy individuals at-risk for colon cancer. This trial provided a unique source of potentially effective and safe immunotherapeutic drugs, fully-human antibodies affinity-matured in a healthy host to a tumor antigen. We purified, cloned, and characterized 13 IgGs specific for several tumor-associated MUC1 epitopes with a wide range of binding affinities. These antibodies bind hypoglycosylated MUC1 on human cancer cell lines and tumor tissues but show no reactivity against fully-glycosylated MUC1 on normal cells and tissues. We found that several antibodies activate complement-mediated cytotoxicity and that T cells carrying chimeric antigen receptors with the antibody variable regions kill MUC1+ target cells, express activation markers, and produce interferon gamma. Fully-human and tumor-specific, these antibodies are candidates for further testing and development as immunotherapeutic drugs.
Identifier: 10.1038/srep31740 (doi), http://www.nature.com/articles/srep31740 (uri), FAUIR000012 (IID)
Persistent Link to This Record: http://purl.flvc.org/fau/fd/FAUIR000012
Use and Reproduction: publisher
Owner Institution: FAU
Is Part Of: Scientific Reports.
2045-2322