Novel Anti-EPHA2 Antibody, DS-8895a for Cancer Treatment

Overview

Journal Cancer Biol Ther

Specialties Oncology
Pharmacology

Date 2016 Sep 23

PMID 27653549

Citations 27

Authors

Jun Hasegawa

Mayumi Sue

Michiko Yamato

Junya Ichikawa

Saori Ishida

Tomoko Shibutani

Michiko Kitamura

Teiji Wada

Toshinori Agatsuma

Affiliations

Soon will be listed here.

Abstract

Overexpression of EPHA2 has been observed in multiple cancers and reported to be associated with poor prognosis. Here, we produced an afucosylated humanized anti-EPHA2 monoclonal antibody (mAb), DS-8895a for cancer treatment. The antibody recognizes the extracellular juxtamembrane region of EPHA2 and therefore can bind to both full-length and truncated forms of EPHA2, which are anchored to cell membranes and recently reported to be produced by post-translational cleavage in tumors. DS-8895a exhibited markedly increased antibody dependent cellular cytotoxicity (ADCC) in vitro and also inhibited tumor growth in EPHA2-positive human breast cancer MDA-MB-231 and human gastric cancer SNU-16 xenograft mouse models. Moreover, DS-8895a in combination with cisplatin (CDDP) showed better efficacy than each of the monotherapies did in the human gastric cancer model. These results suggest that a novel antibody, DS-8895a has therapeutic potential against EPHA2-expressing tumors.

Citing Articles

EphA2 in Cancer: Molecular Complexity and Therapeutic Opportunities.

Toracchio L, Carrabotta M, Mancarella C, Morrione A, Scotlandi K Int J Mol Sci. 2024; 25(22).

PMID: 39596256 PMC: 11594831. DOI: 10.3390/ijms252212191.

Erythropoietin-induced hepatocyte receptor A2 regulates effect of pyroptosis on gastrointestinal colorectal cancer occurrence and metastasis resistance.

Zhang Y, Shi R, Meng R, Lin S, Zheng M World J Gastrointest Oncol. 2024; 16(9):3781-3797.

PMID: 39350985 PMC: 11438782. DOI: 10.4251/wjgo.v16.i9.3781.

Targeting the EphA2 pathway: could it be the way for bone sarcomas?.

Giordano G, Tucciarello C, Merlini A, Cutrupi S, Pignochino Y Cell Commun Signal. 2024; 22(1):433.

PMID: 39252029 PMC: 11382444. DOI: 10.1186/s12964-024-01811-7.

The EphA2 Receptor Regulates Invasiveness and Drug Sensitivity in Canine and Human Osteosarcoma Cells.

Harris E, Sharpe J, Strozen T, Abdi S, Kliewer M, Sanchez M Cells. 2024; 13(14.

PMID: 39056783 PMC: 11275032. DOI: 10.3390/cells13141201.

Ephs in cancer progression: complexity and context-dependent nature in signaling, angiogenesis and immunity.

Guo X, Yang Y, Tang J, Xiang J Cell Commun Signal. 2024; 22(1):299.

PMID: 38811954 PMC: 11137953. DOI: 10.1186/s12964-024-01580-3.

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