Ad5/3 is able to avoid neutralization by binding to erythrocytes and lymphocytes.


Journal

Cancer gene therapy
ISSN: 1476-5500
Titre abrégé: Cancer Gene Ther
Pays: England
ID NLM: 9432230

Informations de publication

Date de publication:
05 2021
Historique:
received: 02 07 2020
accepted: 02 09 2020
revised: 24 08 2020
pubmed: 14 9 2020
medline: 1 2 2022
entrez: 13 9 2020
Statut: ppublish

Résumé

Oncolytic adenoviruses are promising cancer therapeutic agents. Clinical data have shown adenoviruses' ability to transduce tumors after systemic delivery in human cancer patients, despite antibodies. In the present work, we have focused on the interaction of a chimeric adenovirus Ad5/3 with human lymphocytes and human erythrocytes. Ad5/3 binding with human lymphocytes and erythrocytes was observed to occur in a reversible manner, which allowed viral transduction of tumors, and oncolytic potency of Ad5/3 in vitro and in vivo, with or without neutralizing antibodies. Immunodeficient mice bearing xenograft tumors showed enhanced tumor transduction following systemic administration, when Ad5/3 virus was bound to lymphocytes or erythrocytes (P < 0.05). In conclusion, our findings reveal that chimeric Ad5/3 adenovirus reaches non-injected tumors in the presence of neutralizing antibodies: it occurs through reversible binding to lymphocytes and erythrocytes.

Identifiants

pubmed: 32920593
doi: 10.1038/s41417-020-00226-z
pii: 10.1038/s41417-020-00226-z
pmc: PMC8119244
doi:

Substances chimiques

Antibodies, Neutralizing 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

442-454

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Auteurs

Sadia Zafar (S)

Cancer Gene Therapy Group, Translational Immunology Research Program and Department of Oncology, University of Helsinki, Helsinki, Finland.

Dafne Carolina Alves Quixabeira (DCA)

Cancer Gene Therapy Group, Translational Immunology Research Program and Department of Oncology, University of Helsinki, Helsinki, Finland.

Tatiana Viktorovna Kudling (TV)

Cancer Gene Therapy Group, Translational Immunology Research Program and Department of Oncology, University of Helsinki, Helsinki, Finland.

Victor Cervera-Carrascon (V)

Cancer Gene Therapy Group, Translational Immunology Research Program and Department of Oncology, University of Helsinki, Helsinki, Finland.
TILT Biotherapeutics Ltd, Helsinki, Finland.

Joao Manuel Santos (JM)

Cancer Gene Therapy Group, Translational Immunology Research Program and Department of Oncology, University of Helsinki, Helsinki, Finland.
TILT Biotherapeutics Ltd, Helsinki, Finland.

Susanna Grönberg-Vähä-Koskela (S)

Cancer Gene Therapy Group, Translational Immunology Research Program and Department of Oncology, University of Helsinki, Helsinki, Finland.

Fang Zhao (F)

Advanced Microscopy Unit (AMU), Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Pasi Aronen (P)

Biostatistics Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland.

Camilla Heiniö (C)

Cancer Gene Therapy Group, Translational Immunology Research Program and Department of Oncology, University of Helsinki, Helsinki, Finland.

Riikka Havunen (R)

Cancer Gene Therapy Group, Translational Immunology Research Program and Department of Oncology, University of Helsinki, Helsinki, Finland.
TILT Biotherapeutics Ltd, Helsinki, Finland.

Suvi Sorsa (S)

Cancer Gene Therapy Group, Translational Immunology Research Program and Department of Oncology, University of Helsinki, Helsinki, Finland.
TILT Biotherapeutics Ltd, Helsinki, Finland.

Anna Kanerva (A)

Cancer Gene Therapy Group, Translational Immunology Research Program and Department of Oncology, University of Helsinki, Helsinki, Finland.
Department of Obstetrics and Gynecology, Helsinki University Hospital, Helsinki, Finland.

Akseli Hemminki (A)

Cancer Gene Therapy Group, Translational Immunology Research Program and Department of Oncology, University of Helsinki, Helsinki, Finland. akseli.hemminki@helsinki.fi.
TILT Biotherapeutics Ltd, Helsinki, Finland. akseli.hemminki@helsinki.fi.
Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland. akseli.hemminki@helsinki.fi.

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Classifications MeSH