Anti-SSTR2 antibody-drug conjugate for neuroendocrine tumor therapy.

Cancer Gene Therapy
Yingnan SiXiaoguang Liu

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-therapeuti...Continue Reading

References

Jul 11, 1998·Journal of the American College of Surgeons·H ChenM A Choti
Dec 3, 1998·Journal of Gastrointestinal Surgery : Official Journal of the Society for Surgery of the Alimentary Tract·H ChenM A Choti
May 6, 1999·Journal of Vascular and Interventional Radiology : JVIR·K T BrownL H Blumgart
Aug 1, 2000·Immunology Today·M LittleG Moldenhauer
Apr 6, 2001·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·H KiarisG Halmos
May 16, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Anka ThiesUdo Schumacher
Jun 22, 2002·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M HejnaM Raderer
Dec 20, 2002·Proceedings of the National Academy of Sciences of the United States of America·Julie GuillermetCorinne Bousquet
May 21, 2004·Annals of Oncology : Official Journal of the European Society for Medical Oncology·K ObergB Wiedenmann
May 22, 2004·Annals of the New York Academy of Sciences·Hicham LahlouChristiane Susini
May 25, 2005·Annals of Surgery·J Philip BoudreauxWilfrido Castaneda
Sep 27, 2005·Best Practice & Research. Clinical Gastroenterology·Jeffrey A Norton
Dec 17, 2005·Current Opinion in Oncology·Alysandra Lal, Herbert Chen
Feb 12, 2008·Journal of Surgical Oncology·Herbert Chen
Jun 21, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·James C YaoDouglas B Evans
Jul 12, 2008·The Oncologist·Joel T AdlerStan B Sidhu
Dec 19, 2008·The Oncologist·Scott N PinchotHerbert Chen
Sep 18, 2009·Annals of Oncology : Official Journal of the European Society for Medical Oncology·L RighiM Papotti
Jul 16, 2010·Journal of Cellular and Molecular Medicine·Mehtap CakirAshley Grossman
Nov 3, 2010·Current Drug Delivery·Li-Chun Sun, David H Coy
Jun 9, 2012·Journal of the National Comprehensive Cancer Network : JNCCN·Matthew H KulkeUNKNOWN National Comprehensive Cancer Networks
Aug 6, 2013·Methods in Molecular Biology·Bernhard Stump, Jessica Steinmann
Oct 19, 2013·Cancer Cell·Karine PozoJames A Bibb
Feb 26, 2014·The Journal of Surgical Research·Scott K ShermanJames R Howe
Jul 13, 2014·Cancer Letters·Lufang ZhouXiaoguang Margaret Liu
Oct 16, 2015·Clinical Nuclear Medicine·Marleen MelisRichard P Baum
Jan 1, 2016·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Satoshi ShibaTakuji Okusaka
Jan 29, 2016·Journal of the National Cancer Institute·Hanren DaiWeidong Han
Feb 6, 2016·International Journal of Molecular Sciences·Houzong YaoGe Zhang
Mar 12, 2016·Science China. Life Sciences·Bing-Lan ZhangYu-Quan Wei
Jun 15, 2016·Journal of Immunology Research·Hilde AlmåsbakMohan C Vemuri
Jun 22, 2016·The Prostate·David CunninghamZongbing You
Nov 15, 2016·The Journal of Clinical Investigation·Daniel W SherbenouBin Liu
Jan 11, 2018·Nuclear Medicine Review. Central & Eastern Europe·Ismet SarikayaSaud Alenezi

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Citations

Feb 4, 2021·Engineering in Life Sciences·Yingnan SiXiaoguang Margaret Liu
Mar 7, 2021·Molecular and Cellular Endocrinology·E VitaliA G Lania
Apr 1, 2021·Current Treatment Options in Oncology·Alejandro Garcia-AlvarezJaume Capdevila
Apr 3, 2021·Frontiers in Endocrinology·Bilal Haider ShamsiXue Qun Chen
May 9, 2021·Cancer Gene Therapy·Georgios Giamas, Teresa Gagliano
Jun 3, 2021·Pharmaceuticals·Kai ChenXiaoguang Margaret Liu
Aug 8, 2021·Cancers·Yingnan SiXiaoguang Margaret Liu

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