In vitro and in vivo efficacy of an anti-CD203c conjugated antibody (AGS-16C3F) in mouse models of advanced systemic mastocytosis

Blood Advances
Yanyan ZhangFawzia Louache

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
Jun 9, 2007·British Journal of Haematology·Alberto OrfaoUNKNOWN REMA
Jan 16, 2009·International Journal of Immunopathology and Pharmacology·A W HauswirthP Valent
Apr 5, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Danielle Morse, Bakhos A Tannous
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 11, 2015·European Journal of Haematology·Michel ArockPeter 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 21, 2016·American Journal of Hematology·Animesh Pardanani
Sep 26, 2017·Annals of Oncology : Official Journal of the European Society for Medical Oncology·P ValentJ Gotlib

❮ Previous
Next ❯

Related Concepts

Related Feeds

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.