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Internalization of CD239 highly expressed in breast cancer cells: a potential antigen for antibody-drug conjugates.

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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Kikkawa Y,Enomoto-Okawa Y,Fujiyama A,Fukuhara T,Harashima N,Sugawara Y,Negishi Y,Katagiri F,Hozumi K,Nomizu M,Ito Y

doi

10.1038/s41598-018-24961-4

subject

Has Abstract

pub_date

2018-04-26 00:00:00

pages

6612

issue

1

issn

2045-2322

pii

10.1038/s41598-018-24961-4

journal_volume

8

pub_type

杂志文章

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