Optimal Efficacy and Safety of Humanized Anti-Scg3 Antibody to Alleviate Oxygen-Induced Retinopathy

Int J Mol Sci. 2021 Dec 29;23(1):350. doi: 10.3390/ijms23010350.

Abstract

The retinopathy of prematurity (ROP), a neovascular retinal disorder presenting in premature infants, is the leading causes of blindness in children. Currently, there is no approved drug therapy for ROP in the U.S., highlighting the urgent unmet clinical need for a novel therapeutic to treat the disease. Secretogranin III (Scg3) was recently identified as a disease-selective angiogenic factor, and Scg3-neutralizing monoclonal antibodies were reported to alleviate pathological retinal neovascularization in mouse models. In this study, we characterized the efficacy and safety of a full-length humanized anti-Scg3 antibody (hAb) to ameliorate retinal pathology in oxygen-induced retinopathy (OIR) mice, a surrogate model of ROP, by implementing histological and functional analyses. Our results demonstrate that the anti-Scg3 hAb outperforms the vascular endothelial growth factor inhibitor aflibercept in terms of efficacy and safety to treat OIR mice. Our findings support the development of anti-Scg3 hAb for clinical application.

Keywords: Scg3; aflibercept; anti-Scg3 therapy; anti-VEGF; anti-angiogenic therapy; humanized antibody; oxygen-induced retinopathy; retinopathy of prematurity; safety; secretogranin III.

MeSH terms

  • Animals
  • Animals, Newborn
  • Antibodies / administration & dosage
  • Antibodies / therapeutic use*
  • Chromogranins / immunology*
  • Humans
  • Intravitreal Injections
  • Mice
  • Mice, Inbred C57BL
  • Oxygen
  • Retinal Diseases / drug therapy*
  • Retinal Diseases / immunology*
  • Retinal Diseases / physiopathology
  • Retinal Neovascularization / pathology
  • Treatment Outcome
  • Vision, Ocular

Substances

  • Antibodies
  • Chromogranins
  • secretogranin 3, mouse
  • Oxygen