Humanized antibody-drug conjugates for Somatostatin receptor 2 (SSTR2)-positive tumor treatment.

Authors

Zhuoxin Zhou, Zhantao Du, Jiashuai Zhang, Anusua Sarkar, Davis Ballard, Natsorn Watcharadulyarat, Selena Khanal, Phoebe Hu, Lufang Zhou, Xiaoguang Liu

Published in

Molecular cancer therapeutics. Jul 15, 2026. Epub Jul 15, 2026.

Abstract

Somatostatin receptor 2 (SSTR2) is overexpressed in neuroendocrine tumors (NETs) and meningiomas. The objective of this study was to develop an SSTR2-targeted therapy to treat both tumors. We developed a humanized anti-SSTR2 monoclonal antibody demonstrating strong cancer cell binding, internalization in cancer cells, and tumor specificity, as evidenced by flow cytometry, confocal microscopy, and live-animal imaging. Antibody-drug conjugates were generated by conjugating the SSTR2 mAb with potent payloads, including monomethyl auristatin F or mertansine. In vitro assessments revealed high cytotoxicity across NET subtypes and meningioma cell lines. In vivo efficacy was confirmed in two mouse models, i.e. subcutaneous NET xenografts and intracranial meningioma xenografts, where treatment inhibited proliferation, induced apoptosis and cell death, exhibited minimal toxicity, and extended survival. The mechanism of action was further elucidated through bulk RNA sequencing after treatment. These findings highlight the therapeutic potential of our humanized SSTR2 mAb for targeted payload delivery in NETs and meningiomas.

PMID:
42456171
Bibliographic data and abstract were imported from PubMed on 16 Jul 2026.

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