Abstract
Antibody-drug conjugates (ADCs) are a new class of therapeutics that use antibodies to deliver potent cytotoxic drugs selectively to cancer cells. CD203c, an ecto-nucleotide pyrophosphatase-phosphodiesterase 3, is overexpressed on neoplastic mast cells (MCs) in systemic mastocytosis (SM), thus representing a promising target for antibody-mediated therapy. In this study, we have found that human neoplastic MC lines (ROSAKIT D816V and ROSAKIT D816V-Gluc), which express high levels of CD203c, are highly and specifically sensitive to the antiproliferative effects of an ADC against CD203c (AGS-16C3F). In these cell lines, AGS-16C3F induced cell apoptosis at very low concentrations. To characterize the effects of AGS-16C3F on leukemia progression in vivo, ROSAKIT D816V-Gluc NOD-SCID γ mouse models of advanced SM (AdvSM) were treated with AGS-16C3F or an ADC control for 2 weeks. Whereas AGS-16C3F had no apparent toxicity in xenotransplanted mice, in vivo neoplastic MC burden significantly decreased in both hematopoietic and nonhematopoietic organs. Furthermore, animals treated with AGS-16C3F had prolonged survival compared with the animals treated with control ADC, and AGS-16C3F efficiently prevented disease relapse. In conclusion, th...Continue Reading
References
May 1, 1994·Scandinavian Journal of Immunology·G NilssonL Hellman
Apr 10, 2004·Cancer Letters·Yoshihiko YanoMasato Kasuga
Feb 28, 2007·Leukemia & Lymphoma·Anne Staal-ViliareYves Rio
Jun 9, 2007·British Journal of Haematology·Alberto OrfaoUNKNOWN REMA
Jan 16, 2009·International Journal of Immunopathology and Pharmacology·A W HauswirthP Valent
Aug 24, 2010·Breast Cancer Research and Treatment·Teemu T JunttilaMark X Sliwkowski
Apr 5, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Danielle Morse, Bakhos A Tannous
Oct 5, 2012·Cell Death & Disease·Y ZhangF Louache
Oct 10, 2012·Annual Review of Medicine·Eric L Sievers, Peter D Senter
Nov 24, 2012·British Journal of Clinical Pharmacology·John M Lambert
Jan 16, 2014·MAbs·Alain Beck, Janice M Reichert
Mar 29, 2014·Blood·Rosine SalehMichel Arock
May 20, 2014·Allergy·P ValentM Arock
Feb 5, 2015·Leukemia·M ArockP Valent
Feb 19, 2015·Immunity·Shih Han TsaiKiyoshi Takeda
Mar 11, 2015·European Journal of Haematology·Michel ArockPeter Valent
Jun 10, 2015·Leukemia·G WedehP Valent
Jun 28, 2015·Biologicals : Journal of the International Association of Biological Standardization·Gregory S Hamilton
Nov 22, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Fernando DonateDavid R Stover
May 1, 2016·Seminars in Immunopathology·Shih Han Tsai, Kiyoshi Takeda
Jun 15, 2016·The Lancet Oncology·Anish ThomasRaffit Hassan
Oct 4, 2016·Haematologica·Celalettin UstunPeter Valent
Oct 21, 2016·American Journal of Hematology·Animesh Pardanani
Oct 27, 2016·Oncotarget·Siham BibiMichel Arock
Mar 4, 2017·Cancer Research·Peter ValentDean D Metcalfe
Sep 26, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·P ValentJ Gotlib