Anti-SSTR2 antibody-drug conjugate for neuroendocrine tumor therapy.
Journal
Cancer gene therapy
ISSN: 1476-5500
Titre abrégé: Cancer Gene Ther
Pays: England
ID NLM: 9432230
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
01
04
2020
accepted:
24
06
2020
revised:
18
06
2020
pubmed:
21
7
2020
medline:
23
2
2022
entrez:
21
7
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32684623
doi: 10.1038/s41417-020-0196-5
pii: 10.1038/s41417-020-0196-5
pmc: PMC7854894
mid: NIHMS1607243
doi:
Substances chimiques
Immunoconjugates
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
799-812Subventions
Organisme : NHLBI NIH HHS
ID : R21 HL127599
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA238273
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA245580
Pays : United States
Organisme : NCI NIH HHS
ID : R21 CA226491
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA013148
Pays : United States
Informations de copyright
© 2020. The Author(s), under exclusive licence to Springer Nature America, Inc.
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