RRC ID |
51309
|
著者 |
Kikkawa Y, Enomoto-Okawa Y, Fujiyama A, Fukuhara T, Harashima N, Sugawara Y, Negishi Y, Katagiri F, Hozumi K, Nomizu M, Ito Y.
|
タイトル |
Internalization of CD239 highly expressed in breast cancer cells: a potential antigen for antibody-drug conjugates.
|
ジャーナル |
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.
|
巻・号 |
8(1)
|
ページ |
6612
|
公開日 |
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
|
引用数 |
3
|
リソース情報 |
遺伝子材料 |
pFLAG-CMV-2-WT-human Akt2 (RDB06615). |