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Biomedicines 2016, 4(1), 6; doi:10.3390/biomedicines4010006

Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques

1
University Health Network (UHN), Toronto, ON M5G 2C4, Canada
2
Radiation Medicine Program, Princess Margaret Hospital, UHN, Toronto, ON M5G 2M9, Canada
3
Animal Resources Centre, UHN, Toronto, ON M5G 1L7, Canada
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Vincenzo Cerullo
Received: 31 August 2015 / Revised: 27 January 2016 / Accepted: 2 February 2016 / Published: 19 February 2016
(This article belongs to the Special Issue Dendritic Cells and Cancer Immunotherapy)
View Full-Text   |   Download PDF [5533 KB, uploaded 19 February 2016]   |  

Abstract

Anti-cancer immunotherapy is emerging from a nadir and demonstrating tangible benefits to patients. A variety of approaches are now employed. We are invoking antigen (Ag)-specific responses through direct injections of recombinant lentivectors (LVs) that encode sequences for tumor-associated antigens into multiple lymph nodes to optimize immune presentation/stimulation. Here we first demonstrate the effectiveness and antigen-specificity of this approach in mice challenged with prostate-specific antigen (PSA)-expressing tumor cells. Next we tested the safety and efficacy of this approach in two cohorts of rhesus macaques as a prelude to a clinical trial application. Our vector encodes the cDNA for rhesus macaque PSA and a rhesus macaque cell surface marker to facilitate vector titering and tracking. We utilized two independent injection schemas demarcated by the timing of LV administration. In both cohorts we observed marked tissue-specific responses as measured by clinical evaluations and magnetic resonance imaging of the prostate gland. Tissue-specific responses were sustained for up to six months—the end-point of the study. Control animals immunized against an irrelevant Ag were unaffected. We did not observe vector spread in test or control animals or perturbations of systemic immune parameters. This approach thus offers an “off-the-shelf” anti-cancer vaccine that could be made at large scale and injected into patients—even on an out-patient basis. View Full-Text
Keywords: preclinical; lentivector; immunotherapy; cancer vaccine; prostate cancer preclinical; lentivector; immunotherapy; cancer vaccine; prostate cancer
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Au, B.C.; Lee, C.-J.; Lopez-Perez, O.; Foltz, W.; Felizardo, T.C.; Wang, J.C.; Huang, J.; Fan, X.; Madden, M.; Goldstein, A.; Jaffray, D.A.; Moloo, B.; McCart, J.A.; Medin, J.A. Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques. Biomedicines 2016, 4, 6.

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