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Novel anti-EPHA2 antibody, DS-8895a for cancer treatment
Jun Hasegawa1, Mayumi Sue1, Michiko Yamato1
1a Biologics & Immuno-Oncology Laboratories , Daiichi Sankyo Co., Ltd., Shinagawa-ku, Tokyo , Japan.
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.
Insights
A novel afucosylated antibody, DS-8895a, targets EPHA2 overexpression in cancers. This antibody enhances cancer cell killing and inhibits tumor growth, showing therapeutic potential for EPHA2-expressing tumors.
Area of Science:
- Oncology
- Immunology
- Biotechnology
Background:
- Ephrin receptor A2 (EPHA2) overexpression is linked to poor prognosis in various cancers.
- Targeting EPHA2 presents a potential therapeutic strategy for cancer treatment.
Purpose of the Study:
- To develop and evaluate an afucosylated humanized anti-EPHA2 monoclonal antibody (mAb), DS-8895a, for cancer therapy.
- To assess the efficacy of DS-8895a in preclinical cancer models.
Main Methods:
- Production of an afucosylated humanized anti-EPHA2 mAb (DS-8895a).
- Evaluation of DS-8895a's binding to full-length and truncated EPHA2.
- Assessment of DS-8895a-mediated antibody-dependent cellular cytotoxicity (ADCC) in vitro.
- Inhibition of tumor growth in EPHA2-positive human breast and gastric cancer xenograft mouse models.
Main Results:
- DS-8895a demonstrated significantly enhanced ADCC in vitro.
- DS-8895a inhibited tumor growth in both breast and gastric cancer xenograft models.
- Combination therapy with DS-8895a and cisplatin (CDDP) showed superior efficacy compared to monotherapies in gastric cancer models.
Conclusions:
- DS-8895a exhibits potent anti-tumor activity through enhanced ADCC.
- DS-8895a demonstrates therapeutic potential for treating EPHA2-expressing tumors.
- Combination strategies involving DS-8895a may improve treatment outcomes.
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