Future considerations for dendritic cell immunotherapy against chronic viral infections

Abstract

Dendritic cells (DCs) are multifunctional cells that are pivotal in immune defense. As such they have been explored as vaccine carriers, largely in cancer immunotherapy and against some infectious diseases including HIV and viral hepatitis. However, while the use of DCs as vaccine carrier has shown some promise in cancer immunotherapy, this approach is laborious and is subject to strict quality control, which makes it expensive. Furthermore, in some individuals chronically infected with HIV, HCV and/or HBV the numbers of circulating DCs are reduced and/or their functions impaired. In vivo expansion and mobilization of DCs with Flt3L in combination with antigen and/or adjuvant targeting to critical DC receptors may be a more effective approach to control viral replication in chronically infected HIV, HBV and/or HCV patients than current DC immunotherapy approaches.

Keywords::

• dendritic cells
• endocytic receptors
• Flt3L
• HBV immunotherapy
• HCV
• HIV

Acknowledgements

We thank all current and previous members of the laboratory and colleagues at VIDO/Intervac, University of Saskatchewan.

Financial & competing interests disclosure

S van Drunen Littel-van den Hurk and E Atanley are employed by the University of Saskatchewan. Work in S van Drunen Littel-van den Hurk’s laboratory is supported by the Natural Sciences and Engineering Research Council of Canada, Canadian Institutes of Health Research, Saskatchewan Health Research Foundation, Krembil Foundation, Saskatchewan Agriculture, Food and Rural Revitalization, Alberta Livestock Industry Development Fund, Alberta Beef Producers, Agriculture and Food Council of Alberta. VIDO manuscript series number 691. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Globally, millions of people are infected with HBV, HCV or HIV, and as a result, thousands die each year.

• Some chronically infected HBV, HCV and HIV patients fail to develop a sustained response to current treatments.

• Chronic infection with HBV, HCV or HIV may lead to loss of dendritic cells (DCs) and/or their functions, which diminishes downstream immune responses.

• Dendritic cell immunotherapy against HBV, HCV and HIV needs to be improved to achieve superior sustained virologic response.

• Flt3L can induce expansion of myeloid DCs and plasmacytoid DCs, whose roles are important in infectious disease clearance.

• In vivo mobilization and expansion of DCs with Flt3L may be a more effective approach to generate DCs for immunotherapy in chronically infected HBV, HCV and HIV patients with/without DC loss.

• Different DC subsets express distinctive endocytic receptors and initiate different T-cell responses.

• In vivo targeting DCs with antigens and adjuvants via DC endocytic receptors may control viral replication more effectively than current DC immunotherapy approaches.

Notes