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

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 antigen...

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Autores principales: Au, Bryan C., Lee, Chyan-Jang, Lopez-Perez, Orlay, Foltz, Warren, Felizardo, Tania C., Wang, James C.M., Huang, Ju, Fan, Xin, Madden, Melissa, Goldstein, Alyssa, Jaffray, David A., Moloo, Badru, McCart, J. Andrea, Medin, Jeffrey A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344243/
https://www.ncbi.nlm.nih.gov/pubmed/28536373
http://dx.doi.org/10.3390/biomedicines4010006
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author Au, Bryan C.
Lee, Chyan-Jang
Lopez-Perez, Orlay
Foltz, Warren
Felizardo, Tania C.
Wang, James C.M.
Huang, Ju
Fan, Xin
Madden, Melissa
Goldstein, Alyssa
Jaffray, David A.
Moloo, Badru
McCart, J. Andrea
Medin, Jeffrey A.
author_facet Au, Bryan C.
Lee, Chyan-Jang
Lopez-Perez, Orlay
Foltz, Warren
Felizardo, Tania C.
Wang, James C.M.
Huang, Ju
Fan, Xin
Madden, Melissa
Goldstein, Alyssa
Jaffray, David A.
Moloo, Badru
McCart, J. Andrea
Medin, Jeffrey A.
author_sort Au, Bryan C.
collection PubMed
description 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.
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spelling pubmed-53442432017-05-23 Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques Au, Bryan C. Lee, Chyan-Jang Lopez-Perez, Orlay Foltz, Warren Felizardo, Tania C. Wang, James C.M. Huang, Ju Fan, Xin Madden, Melissa Goldstein, Alyssa Jaffray, David A. Moloo, Badru McCart, J. Andrea Medin, Jeffrey A. Biomedicines Article 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. MDPI 2016-02-19 /pmc/articles/PMC5344243/ /pubmed/28536373 http://dx.doi.org/10.3390/biomedicines4010006 Text en © 2015 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Au, Bryan C.
Lee, Chyan-Jang
Lopez-Perez, Orlay
Foltz, Warren
Felizardo, Tania C.
Wang, James C.M.
Huang, Ju
Fan, Xin
Madden, Melissa
Goldstein, Alyssa
Jaffray, David A.
Moloo, Badru
McCart, J. Andrea
Medin, Jeffrey A.
Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques
title Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques
title_full Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques
title_fullStr Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques
title_full_unstemmed Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques
title_short Direct Lymph Node Vaccination of Lentivector/Prostate-Specific Antigen is Safe and Generates Tissue-Specific Responses in Rhesus Macaques
title_sort direct lymph node vaccination of lentivector/prostate-specific antigen is safe and generates tissue-specific responses in rhesus macaques
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5344243/
https://www.ncbi.nlm.nih.gov/pubmed/28536373
http://dx.doi.org/10.3390/biomedicines4010006
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