Human anti-MUC1 antibodies elicited by a prophylactic cancer vaccine for mAb and CAR-modified T cell immunotherapies (VAC11P.1004)

Abstract

Abstract MUC1 is a tumor-associated protein that is abnormally expressed on all human adenocarcinomas. In our recent clinical trial, individuals at-risk for colonic adenoma received a prophylactic MUC1 cancer vaccine. Many individuals responded by producing high-affinity anti-MUC1 antibodies. We isolated a panel of these antibodies and seek to develop them as antibody and CAR T cell cancer immunotherapies. Our collaborators used a novel method combining proteomics and next-gen DNA sequencing to identify and recombinantly produce 12 high-affinity antibodies from the sera of vaccinated individuals. By ELISA we determined that the antibodies bind with high-affinity to diverse epitopes within the MUC1 vaccine peptide. We also found that several of the antibodies can stain MUC1+ pancreas, colon, and breast cancer cell lines but not a cell line expressing normal MUC1. We then determined that the antibodies could stain MUC1+ human pancreas and colon tumor samples but not normal tissues. Having established tumor-specificity we are now assessing the antibodies in a series of functional assays. Finally, we have constructed CAR lentiviral constructs using the variable regions of the antibodies as targeting domains and are testing their ability to mediate MUC1-specific target cell lysis. As the antibodies are human-derived, indication of efficacy in pre-clinical testing has the potential to directly enable clinical trials and hopefully approval of these reagents for therapy of cancer patients.