Anti-SSTR2 antibody-drug conjugate for neuroendocrine tumor therapy

Yingnan Si, Seulhee Kim, Jianfa Ou, Yun Lu, Patrick Ernst, Kai Chen, Jason Whitt, Angela M. Carter, James M. Markert, James A. Bibb, Herbert Chen, Lufang Zhou, Renata Jaskula-Sztul, Xiaoguang “Margaret” Liu

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Neuroendocrine (NE) tumors include a diverse spectrum of hormone-secreting neoplasms that arise from the endocrine and nervous systems. Current chemo- and radio-therapies have marginal curative benefits. The goal of this study was to develop an innovative antibody-drug conjugate (ADC) to effectively treat NE tumors (NETs). First, we confirmed that somatostatin receptor 2 (SSTR2) is an ideal cancer cell surface target by analyzing 38 patient-derived NET tissues, 33 normal organs, and three NET cell lines. Then, we developed a new monoclonal antibody (mAb, IgG1, and kappa) to target two extracellular domains of SSTR2, which showed strong and specific surface binding to NETs. The ADC was constructed by conjugating the anti-SSTR2 mAb and antimitotic monomethyl auristatin E. In vitro evaluations indicated that the ADC can effectively bind, internalize, release payload, and kill NET cells. Finally, the ADC was evaluated in vivo using a NET xenograft mouse model to assess cancer-specific targeting, tolerated dosage, pharmacokinetics, and antitumor efficacy. The anti-SSTR2 ADC exclusively targeted and killed NET cells with minimal toxicity and high stability in vivo. This study demonstrates that the anti-SSTR2 ADC has a high-therapeutic potential for NET therapy.

Original languageEnglish (US)
Pages (from-to)799-812
Number of pages14
JournalCancer Gene Therapy
Volume28
Issue number7-8
DOIs
StatePublished - Aug 2021
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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