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

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.