In:
Cancer Science, Wiley, Vol. 110, No. 2 ( 2019-02), p. 674-685
Abstract:
l ‐Type amino acid transporter 1 ( LAT 1) disulfide linked to CD 98 heavy chain (hc) is highly expressed in most cancer cells, but weakly expressed in normal cells. In the present study, we developed novel anti‐ LAT 1 mA bs and showed internalization activity, inhibitory effects of amino acid uptake and cell growth and antibody‐dependent cellular cytotoxicity, as well as in vivo antitumor effects in athymic mice. Furthermore, we examined the reactivity of mA bs with LAT 1 of Macaca fascicularis to evaluate possible side‐effects of antihuman LAT 1 mA bs in clinical trials. Antihuman LAT 1 mA bs reacted with ACHN human and MK .P3 macaca kidney‐derived cells, and this reactivity was significantly decreased by si RNA s against LAT 1. Macaca LAT 1 cDNA was cloned from MK .P3, and only two amino acid differences between human and macaca LAT 1 were seen. RH 7777 rat hepatoma and HEK 293 human embryonic kidney cells expressing macaca LAT 1 were established as stable transfectants, and antihuman LAT 1 mA bs were equivalently reactive against transfectants expressing human or macaca LAT 1. Dual (high and low) avidity modes were detected in transfectants expressing macaca LAT 1, MK .P3, ACHN and HCT 116 human colon cancer cells, and K A values were increased by anti‐ CD 98hc mA b, suggesting anti‐ LAT 1 mA bs detect an epitope on LAT 1‐ CD 98hc complexes on the cell surface. Based on these results, LAT 1 may be a promising anticancer target and Macaca fascicularis can be used in preclinical studies with antihuman LAT1 mA bs.
Type of Medium:
Online Resource
ISSN:
1347-9032
,
1349-7006
DOI:
10.1111/cas.2019.110.issue-2
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2115647-5
detail.hit.zdb_id:
2111204-6
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