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

• Published in: International journal of molecular sciences Vol. 23; no. 1; p. 350
• Main Authors: He, Ye, Tian, Hong, Dai, Chang, Wen, Rong, Li, Xiaorong, Webster, Keith A, Li, Wei
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.12.2021; MDPI
• Subjects: Angiogenesis; Animal models; Animals; Animals, Newborn; anti-angiogenic therapy; anti-Scg3 therapy; Antibodies - administration & dosage; Antibodies - therapeutic use; Blindness; Chromogranins - immunology; Diabetic retinopathy; Disease; Drug dosages; Drug therapy; Growth factors; Humans; Intravitreal Injections; Kidneys; Light; Mice; Mice, Inbred C57BL; Monoclonal antibodies; Oxygen; oxygen-induced retinopathy; Physiology; Premature babies; Premature birth; Retina; Retinal Diseases - drug therapy; Retinal Diseases - immunology; Retinal Diseases - physiopathology; Retinal Neovascularization - pathology; Retinopathy; retinopathy of prematurity; Safety; Scg3; secretogranin III; Treatment Outcome; Vascular endothelial growth factor; Vascularization; Vision, Ocular; anti-angiogenic therapy; anti-Scg3 therapy; aflibercept; safety; secretogranin III; anti-VEGF; Scg3; oxygen-induced retinopathy; retinopathy of prematurity; humanized antibody
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23010350

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.