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    MUC1-C INTEGRATES CHRONIC ACTIVATION OF INTERFERON PATHWAYS WITH CHROMATIN REMODELING IN TREATMENT RESISTANCE OF TRIPLE-NEGATIVE BREAST CANCER (SABCS 2023)
    In support of these results, targeting MUC1-C in wild-type BRCA1/2 TNBC cells enhanced carboplatin-induced DNA damage and loss of self- renewal capacity. In addition, MUC1-C was necessary for DNA damage resistance, self-renewal and tumorigenicity of olaparib-resistant BRCA1-mutant TNBC cells...As one example, an allogeneic anti-MUC1-C CAR T cell using MAb 3D1 sequences is undergoing Phase I evaluation for the treatment of MUC1-C-expressing cancers (NCT05239143: P-MUC1C-ALLO1 Allogeneic CAR-T Cells in the Treatment of Subjects with Advanced or Metastatic Solid Tumors). In addition, anti-MUC1-C huMAb3D1-MMAE ADCs are under development by the NCI NExT Program for IND-enabling studies and performing early phase clinical trials in patients with TNBC.
    BRCA Biomarker • PARP Biomarker • IO biomarker
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PBRM1 (Polybromo 1) • MUC1 (Mucin 1) • IDO1 (Indoleamine 2,3-dioxygenase 1) • STING (stimulator of interferon response cGAMP interactor 1) • IRF1 (Interferon Regulatory Factor 1) • STAT1 (Signal Transducer And Activator Of Transcription 1) • IFIH1 (Interferon Induced With Helicase C Domain 1)
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    BRCA1 mutation • BRCA wild-type • PBRM1 mutation • MUC1 expression • IRF1 expression
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    Lynparza (olaparib) • carboplatin • P-MUC1C-ALLO1
    over1year
    Development of an allogeneic CAR-T targeting MUC1-C (MUC1, cell surface associated, C-terminal) for epithelial derived tumors (ESMO-IO 2022)
    In early phase I experience, P-MUC1C-ALLO1 is safe and tolerable with an early signal of efficacy at a low starting dose. P-MUC1C-ALLO1 phase I trial enrollment is on-going.
    IO biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • MUC1 (Mucin 1)
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    MUC1 expression
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    P-MUC1C-ALLO1