CAR T Cells Targeting the Tumor MUC1 Glycoprotein Reduce Triple-Negative Breast Cancer Growth

Ru Zhou, Mahboubeh Yazdanifar, Lopamudra Das Roy, Lynsey M. Whilding, Artemis Gavrill, John Maher, Pinku Mukherjee

Research output: Contribution to journalArticlepeer-review

117 Citations (Scopus)

Abstract

Antibody-derived chimeric antigen receptor (CAR) T cell therapy has achieved gratifying breakthrough in hematologic malignancies but has shown limited success in solid tumor immunotherapy. Monoclonal antibody, TAB004, specifically recognizes the aberrantly glycosylated tumor form of MUC1 (tMUC1) in all subtypes of breast cancer including 95% of triple-negative breast cancer (TNBC) while sparing recognition of normal tissue MUC1. We transduced human T cells with MUC28z, a chimeric antigen receptor comprising of the scFv of TAB004 coupled to CD28 and CD3ζ. MUC28z was well-expressed on the surface of engineered activated human T cells. MUC28z CAR T cells demonstrated significant target-specific cytotoxicity against a panel of human TNBC cells. Upon recognition of tMUC1 on TNBC cells, MUC28z CAR T cells increased production of Granzyme B, IFN-γ and other Th1 type cytokines and chemokines. A single dose of MUC28z CAR T cells significantly reduced TNBC tumor growth in a xenograft model. Thus, MUC28z CAR T cells have high therapeutic potential against tMUC1-positive TNBC tumors with minimal damage to normal breast epithelial cells.

Original languageEnglish
Article number1149
Number of pages1
JournalFrontiers in Immunology
Volume10
Issue numberMAY
DOIs
Publication statusPublished - 1 Jan 2019

Keywords

  • Immunotherapy
  • MUC1
  • MUC28z CAR T cells
  • TAB004
  • Triple-negative breast cancer

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