Developing a CAR-T that targets human Tn-MUC1 in solid cancers

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B953
Abstract ID: 6490

Presenting Author:
Diana Rose E Ranoa , Postdoctoral Scholar at Univ. of Illinois, Urbana-Champaign

Abstract:

Chimeric antigen receptor T cell (CAR-T) therapy has been proven to be successful in patients with B cell lymphomas, yet its efficacy on solid tumors remains challenging. We previously established an immunocompetent murine model to characterize Tn-antigen specific CAR-T cells targeting advanced stages of ID8 ovarian tumors. The CAR contained a single-chain Fv from antibody 237 which recognizes a Tn-glycopeptide-antigen expressed by ID8 due to aberrant O-linked glycosylation in the absence of the chaperone COSMC (C1GALT1C1). TNGK CAR was a derivative of 237 CAR engineered to have higher affinity towards Tn-MUC1 expressed on human tumors. We screened human cell lines with predicted deletion of the C1GALT1C1 gene and found two cell lines strongly positive for Tn-expression, the T-cell lymphoma line Jurkat and the melanoma line LOX-IMVI. Both were recognized by TNGK CAR-T in co-culture experiments, using IL-2 and IFN-γ ELISA-based assays. RNA sequencing confirmed a frameshift deletion of C1GALT1C1 exon 2 in Jurkat and the lack of C1GALT1C1 transcripts in LOX-IMVI. We further queried the TCGA database for the frequency of C1GALT1C1 deep deletions in human cancer patients, and found 2-20% prevalence across different types of cancer, with urinary bladder cancer and soft tissue sarcoma on top. We are currently doing immunohistochemistry of biopsy samples from urinary bladder cancer patients in order to develop an approach that might support a phase I trial.