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Anti-SSTR2 antibody-drug conjugate for neuroendocrine tumor therapy
- Source :
- Cancer gene therapy
- Publication Year :
- 2020
-
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.
- Subjects :
- 0301 basic medicine
Cancer Research
Antibody-drug conjugate
Immunoconjugates
medicine.drug_class
medicine.medical_treatment
Mice, Nude
Monoclonal antibody
Article
Targeted therapy
03 medical and health sciences
Mice
0302 clinical medicine
In vivo
medicine
Somatostatin receptor 2
Animals
Humans
Molecular Biology
Chemistry
In vitro
body regions
Neuroendocrine Tumors
030104 developmental biology
030220 oncology & carcinogenesis
Cancer cell
Cancer research
Molecular Medicine
Conjugate
Subjects
Details
- ISSN :
- 14765500
- Volume :
- 28
- Issue :
- 7-8
- Database :
- OpenAIRE
- Journal :
- Cancer gene therapy
- Accession number :
- edsair.doi.dedup.....2b53eead54b003432e4fbbd9ca136e67