Therapeutics/pharmacology

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Human anti-muc1 Antibodies Elicited by a Prophylactic Cancer Vaccine for Car T Cell and Mab Immunotherapies

Thursday, June 15
5:45 PM - 7:00 PM

Hypoglycosylated MUC1 is a tumor-associated protein that is expressed on over 80% of all human cancers. In our recent clinical trial, individuals at-risk for colonic adenocarcinoma received a prophylactic MUC1 cancer vaccine. Many individuals responded producing high titers of anti-MUC1 IgG antibodies with no detectable toxicity. TCR repertoire sequencing also revealed several differentially abundant T cell clones induced by the vaccine. This trial provided a rare source of human antibodies raised and affinity-matured in a healthy human host to abnormal MUC1. We isolated and identified 13 anti-MUC1 monoclonal antibodies that could bind to several different epitopes on the MUC1 vaccine peptide with a range of affinities. They also stain MUC1 on human cancer cell lines and colon, breast, lung, and pancreas adenocarcinoma tissue sections while showing no reactivity against a large panel of normal tissues. We found that two of the antibodies are capable of performing MUC1-depdendent complement-mediated cytotoxicity (CDC). Next, we constructed a series of lentiviral vectors encoding chimeric antigen receptors (CARs) using scFv’s of the antibodies as antigen binding regions. Several CARs were able to retarget human primary T cells to become activated and produce cytokines in a MUC1-dependent manner, and were able to mediate lysis of MUC1+ human tumor cell lines. Preclinical testing in MUC1.tg mouse tumor graft model is underway. Being of fully human origin and showing a high-degree of tumor specificity and efficacy in preclinical experiments this research has the potential to enable clinical trials needed for approval of these reagents for cancer therapy.

Jason Lohmueller

University of Pittsburgh

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    James D. Ham

    Carnegie Mellon University

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      Olivera Finn

      University of Pittsburgh

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        Human anti-muc1 Antibodies Elicited by a Prophylactic Cancer Vaccine for Car T Cell and Mab Immunotherapies



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