Journal
CANCER GENE THERAPY
Volume 28, Issue 5, Pages 442-454Publisher
SPRINGERNATURE
DOI: 10.1038/s41417-020-00226-z
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Funding
- KLTO (Doctoral School for Clinical Research programme at the University of Helsinki)
- Jane and Aatos Erkko Foundation
- HUCH Research Funds (EVO)
- Sigrid Juselius Foundation
- Finnish Cancer Organizations
- University of Helsinki
- Novo Nordisk Foundation
- Paivikki and Sakari Sohlberg Foundation
- Finnish Society of Sciences And Letters
- TILT Biotherapeutics Ltd
- European Commission Marie Curie Innovative Training Network VIRION [H2020-MSCA-ITN-2014 643130]
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The chimeric Ad5/3 adenovirus can reach non-injected tumors in the presence of neutralizing antibodies by reversibly binding to lymphocytes and erythrocytes, demonstrating good oncolytic efficacy.
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.
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