Unknown

Dataset Information

0

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


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, these preclinical studies identified CD203c as a novel therapeutic target on neoplastic MCs, and AGS-16C3F as a promising ADC for the treatment of patients with AdvSM.

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC6391676 | biostudies-other | 2019 Feb

REPOSITORIES: biostudies-other

Similar Datasets

| S-EPMC6278969 | biostudies-literature
| S-EPMC7572963 | biostudies-literature
| S-EPMC9647833 | biostudies-literature
| S-EPMC6630092 | biostudies-literature
| S-EPMC9084172 | biostudies-literature
| S-EPMC8674134 | biostudies-literature
| S-EPMC6245986 | biostudies-literature
| S-EPMC8674139 | biostudies-literature
| S-EPMC10802166 | biostudies-literature
| S-EPMC6292539 | biostudies-literature