RRC ID 51309
Author Kikkawa Y, Enomoto-Okawa Y, Fujiyama A, Fukuhara T, Harashima N, Sugawara Y, Negishi Y, Katagiri F, Hozumi K, Nomizu M, Ito Y.
Title Internalization of CD239 highly expressed in breast cancer cells: a potential antigen for antibody-drug conjugates.
Journal Sci Rep
Abstract Antibody-drug conjugates (ADCs) are attractive in cancer therapy because they can directly bind to cancer cells and provide anticancer activity. To kill cancer cells with ADCs, the target antigens are required not only to be highly and/or selectively expressed on cancer cells but also internalized by the cells. CD239, also known as the Lutheran blood group glycoprotein (Lu) or basal cell adhesion molecule (B-CAM), is a specific receptor for laminin α5, a major component of basement membranes. Here, we show that CD239 is strongly expressed in a subset of breast cancer cells and internalized into the cells. We also produced a human single-chain variable fragment (scFv) specific to CD239 fused with human IgG1 Fc, called C7-Fc. The binding affinity of the C7-Fc antibody is similar to that of mouse monoclonal antibodies. Although the C7-Fc antibody alone does not influence cellular functions, when conjugated with a fragment of diphtheria toxin lacking the receptor-binding domain (fDT), it can selectively kill breast cancer cells. Interestingly, fDT-bound C7-Fc shows anticancer activity in CD239-highly positive SKBR3 cells, but not in weakly positive cells. Our results show that CD239 is a promising antigen for ADC-based breast cancer therapy.
Volume 8(1)
Pages 6612
Published 2018-4-26
DOI 10.1038/s41598-018-24961-4
PII 10.1038/s41598-018-24961-4
PMID 29700410
PMC PMC5919910
MeSH Animals Biomarkers, Tumor Breast Neoplasms / drug therapy Breast Neoplasms / genetics Breast Neoplasms / metabolism* Breast Neoplasms / pathology Cell Adhesion Molecules / antagonists & inhibitors Cell Adhesion Molecules / genetics Cell Adhesion Molecules / metabolism* Cell Line, Tumor Cytotoxicity Tests, Immunologic Endocytosis* Female Humans Immunoconjugates / pharmacology Immunoglobulin Fc Fragments / immunology Immunohistochemistry Lutheran Blood-Group System / genetics Lutheran Blood-Group System / metabolism* Mice Protein Binding Protein Transport Single-Chain Antibodies / pharmacology
IF 3.998
Times Cited 3
DNA material pFLAG-CMV-2-WT-human Akt2 (RDB06615).