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Targeting polysialic acid-abundant cancers using oncolytic adenoviruses with fibers fused to active bacteriophage borne endosialidase.
Martin, Nikolas T; Wrede, Christoph; Niemann, Julia; Brooks, Jennifer; Schwarzer, David; Kühnel, Florian; Gerardy-Schahn, Rita.
Afiliação
  • Martin NT; Institute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany; REBIRTH Cluster of Excellence, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
  • Wrede C; Institute of Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany; REBIRTH Cluster of Excellence, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
  • Niemann J; Clinic for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
  • Brooks J; Clinic for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
  • Schwarzer D; Institute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
  • Kühnel F; Clinic for Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
  • Gerardy-Schahn R; Institute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany; REBIRTH Cluster of Excellence, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Electronic address: Gerardy-Schahn.Rita@mh-hannover.de.
Biomaterials ; 158: 86-94, 2018 03.
Article em En | MEDLINE | ID: mdl-29304405
Genetic replacement of adenoviral fiber knobs by ligands that enable tumor specific targeting of oncolytic adenoviruses is challenging because the fiber knob contributes to virus assembly. Here, we present a novel concept by describing stable recombinant adenoviruses with tumor specific infection mode. The fiber knob was replaced by endosialidaseNF (endoNF), the tailspike protein of bacteriophage K1F. EndoNF recognizes polysialic acid, an oncofetal antigen characteristic for high malignant tumors of neuroendocrine origin. An intramolecular chaperone contained in endoNF warrants folding and compensates for the knob function in virus assembly. Obtained recombinant viruses demonstrated polysialic acid dependent infection modes, strong oncolytic capacity with polysialic acid positive cells in culture and a high potential to inhibit tumor growth in a therapeutic mouse model of subcutaneous neuroblastoma. With a single genetic manipulation we achieved ablation of the fiber knob, introduction of a tumor specific ligand, and folding control over the chimeric fiber construct.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ácidos Siálicos / Adenoviridae / Vírus Oncolíticos / Terapia Viral Oncolítica / Neoplasias / Neuraminidase Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Ácidos Siálicos / Adenoviridae / Vírus Oncolíticos / Terapia Viral Oncolítica / Neoplasias / Neuraminidase Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2018 Tipo de documento: Article