Intercellular Adhesion Molecule-1 as Target for CAR-T-Cell Therapy of Triple-Negative Breast Cancer

Bibliographic Details
Title: Intercellular Adhesion Molecule-1 as Target for CAR-T-Cell Therapy of Triple-Negative Breast Cancer
Authors: Heng Wei, Zeng Wang, Yi Kuang, Zhiguo Wu, Shasha Zhao, Zongliang Zhang, Hexian Li, Meijun Zheng, Nan Zhang, Cheng Long, Wenhao Guo, Chunlai Nie, Hui Yang, Aiping Tong
Source: Frontiers in Immunology, Vol 11 (2020)
Publisher Information: Frontiers Media S.A., 2020.
Publication Year: 2020
Collection: LCC:Immunologic diseases. Allergy
Subject Terms: triple-negative breast cancer, intercellular adhesion molecule-1, chimeric antigen receptor T cells, immunotherapy, single chain variable fragment, Immunologic diseases. Allergy, RC581-607
More Details: Triple-negative breast cancer (TNBC) comprises lethal malignancies with limited treatment options. Chimeric antigen receptor T (CAR-T) cell therapy is an effective immunotherapeutic strategy that has demonstrated unprecedented efficacy in the treatment of hematological malignancies but has shown limited success in the management of some solid tumors. Many malignant tumors are related to increased expression of intercellular adhesion molecule-1 (ICAM1), providing a rationale for ICAM1-specific immunotherapies for the treatment of cancer. Here, we validated the expression of ICAM1 in TNBC tissues. Subsequently, we generated a phage-displayed single-chain variable fragment (scFv) library using splenocytes from ICAM1-immunized mice and selected a novel ICAM1-specific scFv, mG2-scFv. Using mG2-scFv as the extracellular antigen binding domain, we constructed ICAM1-specific CAR-T cells and demonstrated the robust and specific killing of TNBC cell lines in vitro. Most importantly, in the TNBC mouse model, ICAM1-specific CAR-T cells significantly reduced the growth of the TNBC tumor, resulting in long-term remission and improved survival. Together, these results indicated that ICAM1-specific CAR-T cells have high therapeutic potential against ICAM1-positive TNBC tumors.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1664-3224
Relation: https://www.frontiersin.org/article/10.3389/fimmu.2020.573823/full; https://doaj.org/toc/1664-3224
DOI: 10.3389/fimmu.2020.573823
Access URL: https://doaj.org/article/c470d526e078448c9eaaf71de2f39146
Accession Number: edsdoj.470d526e078448c9eaaf71de2f39146
Database: Directory of Open Access Journals
More Details
ISSN:16643224
DOI:10.3389/fimmu.2020.573823
Published in:Frontiers in Immunology
Language:English