Arcelis™ AGS-004 dendritic cell-based immunotherapy for HIV infection

Abstract

Antiretroviral therapy represents a major breakthrough for the management of HIV-infected patients; however, it is not without side effects and is a life-long commitment. Thus, the development of novel strategies to enhance immune response and control viral replication are needed in order to limit exposure to antiretroviral therapy. To date, immunotherapies consisting of monocyte-derived dendritic cells expressing HIV antigens have elicited only limited immunogenicity and/or viral control. Thus, taking into consideration the variability of HIV, an investigational immunotherapeutic product (AGS-004, Argos Therapeutics Inc., NC, USA) that consists of autologous dendritic cells co-electroporated with in vitro transcribed RNA encoding four of the patient‘s own HIV antigens was developed. Based on the encouraging immunogenicity and tolerance observed in a Phase I study, a Phase II study has been initiated with good tolerance and partial viral control. A second Phase II placebo-controlled study is about to initiate.

KEYWORDS::

• CD40 ligand
• dendritic cell
• HIV
• therapeutic vaccine

Acknowledgements

Irina Tchrepanova, Don Healey, Rafick-Pierre Sekaly, Renu Jain, Mohamed-Rachid Boulassel, Amir Antar, Fanny Morel, Bertrand Lebouché and Rachel Kyle for their invaluable contribution to the development of ASG-004 from the laboratory to the clinic.

Financial & competing interests disclosure

This project has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, NIH and Department of Health and Human Services under Contract No. N01-AI-60019, and by CANVAC (HIV-001), the Canadian Institutes of Health Research (CIHR) Canadian Trials Network (CTN) Studies No. 229 and 239 and Fonds de la Recherche en Santé du Québec (FRSQ). Jean-Pierre Routy is a clinician–scientist supported by FRSQ. 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.

Additional information

Funding

This project has been funded in part with Federal funds from the National Institute of Allergy and Infectious Diseases, NIH and Department of Health and Human Services under Contract No. N01-AI-60019, and by CANVAC (HIV-001), the Canadian Institutes of Health Research (CIHR) Canadian Trials Network (CTN) Studies No. 229 and 239 and Fonds de la Recherche en Santé du Québec (FRSQ). Jean-Pierre Routy is a clinician–scientist supported by FRSQ. 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.