Your browser doesn't support javascript.
loading
Retinal and Lens Degeneration in New Zealand White Rabbits Administered Intravitreal TSG-6 Link Domain-Rabbit FAb Fusion Proteins.
Laing, Steven T; Tassew, Nardos; Tesar, Devin; Wang, Yue; Crowell, Susan R; Gray, Julia; Kwong, Mandy; Loyet, Kelly M; Andaya, Roxanne; Kusi, Aija; Kelley, Robert F.
Afiliación
  • Laing ST; Department of Safety Assessment, 7412Genentech Inc., South San Francisco, CA, USA.
  • Tassew N; Department of Safety Assessment, 7412Genentech Inc., South San Francisco, CA, USA.
  • Tesar D; Department of Pharmaceutical Development, 7412Genentech Inc., South San Francisco, CA, USA.
  • Wang Y; Department of Pharmaceutical Development, 7412Genentech Inc., South San Francisco, CA, USA.
  • Crowell SR; Department of Preclinical and Translational Pharmacokinetics & Pharmacodynamics, 7412Genentech Inc., South San Francisco, CA, USA.
  • Gray J; Department of Biochemical and Cellular Pharmacology, 7412Genentech Inc., South San Francisco, CA, USA.
  • Kwong M; Department of Biochemical and Cellular Pharmacology, 7412Genentech Inc., South San Francisco, CA, USA.
  • Loyet KM; Department of Biochemical and Cellular Pharmacology, 7412Genentech Inc., South San Francisco, CA, USA.
  • Andaya R; Department of Safety Assessment, 7412Genentech Inc., South San Francisco, CA, USA.
  • Kusi A; Department of Safety Assessment, 7412Genentech Inc., South San Francisco, CA, USA.
  • Kelley RF; Department of Pharmaceutical Development, 7412Genentech Inc., South San Francisco, CA, USA.
Toxicol Pathol ; 49(3): 634-646, 2021 04.
Article en En | MEDLINE | ID: mdl-33349160
Fusion of biologic therapeutics to hyaluronic acid binding proteins, such as the link domain (LD) of Tumor necrosis factor (TNF)-Stimulated Gene-6 (TSG-6), is expected to increase vitreous residence time following intravitreal injection and provide for long-acting delivery. The toxicity of a single intravitreal dose of free TSG-6-LD and fusion proteins of TSG-6-LD and a nonbinding rabbit antibody fragment (RabFab) were assessed in New Zealand White rabbits. Animals administered free TSG-6-LD exhibited extensive lens opacities and variable retinal vascular attenuation, correlated with microscopic findings of lens and retinal degeneration. Similar but less severe findings were present in animals dosed with the RabFab-TSG-6-LD fusion proteins. In-life ocular inflammation was noted in all animals from 7-days postdose and was associated with high anti-RabFab antibody titers in animals administered fusion proteins. Inflammation and retinal degeneration were multifocally associated with evidence of retinal detachment, and hypertrophy and migration of vimentin, glial fibrillary acidic protein, and glutamine synthetase positive Müller cells to the outer nuclear layer. Further assessment of alternative hyaluronic acid binding protein fusions should consider the potential for retinal degeneration and enhanced immune responses early in development.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Retina / Degeneración Retiniana Límite: Animals Idioma: En Revista: Toxicol Pathol Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Retina / Degeneración Retiniana Límite: Animals Idioma: En Revista: Toxicol Pathol Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos