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

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...

Full description

Saved in:
Bibliographic Details
Published in:Frontiers in immunology 2019-05, Vol.10, p.1149-1149
Main Authors: Zhou, Ru, Yazdanifar, Mahboubeh, Roy, Lopamudra Das, Whilding, Lynsey M, Gavrill, Artemis, Maher, John, Mukherjee, Pinku
Format: Article
Language:English
Subjects:
Animals
Antigens, Neoplasm - immunology
Cell Line, Tumor
Cytokines - metabolism
Cytotoxicity, Immunologic
Disease Models, Animal
Female
Genetic Engineering
Humans
Immunology
Immunophenotyping
immunotherapy
Immunotherapy, Adoptive - adverse effects
Immunotherapy, Adoptive - methods
Lymphocyte Activation - immunology
Mice
MUC1
MUC28z CAR T cells
Mucin-1 - immunology
Receptors, Chimeric Antigen - genetics
Receptors, Chimeric Antigen - metabolism
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
TAB004
Treatment Outcome
Triple Negative Breast Neoplasms - immunology
Triple Negative Breast Neoplasms - therapy
triple-negative breast cancer
Xenograft Model Antitumor Assays
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2019.01149