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A nanoparticle therapeutic vaccine targeting HAAH stimulates cellular immunity

A nanoparticle therapeutic vaccine targeting HAAH stimulates cellular immunity Lebowitz et al. Journal for ImmunoTherapy of Cancer 2015, 3(Suppl 2):P442 http://www.immunotherapyofcancer.org/content/3/S2/P442 POSTER PRESENTATION Open Access A nanoparticle therapeutic vaccine targeting HAAH stimulates cellular immunity Michael Lebowitz , Solomon Stewart, Susan Walker, Samindhi Wu, Steven Fuller, Hossein Ghanbari From 30th Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2015) National Harbor, MD, USA. 4-8 November 2015 Background assisted cell sorting (MACS, Milltenyi Biotec). CTL We are evaluating the immunogenicity and efficacy of a responses were measured using a fluorescent assay in nanoparticle vaccine (NPV) targeting the tumor marker which target cells were pre-loaded with 5-(6)-carboxy- human aspartyl (asparaginyl) b-hydroxylase (HAAH). fluorescein diacetate succinimidyl ester (CFSE) and dead HAAH is an embryonic protein that is over-expressed cells were labelled after incubation with effector cells on the surface of cancer cells, is demonstrated to be with 7-amino actinomycin D (7-AAD). responsible for cell proliferation, motility and invasive- ness, processes which can be inhibited by anti-HAAH Results antibodies in vitro. We have developed novel anticancer Antigen specific cytotoxic T cell responses were detected NPVs in which portions of the HAAH molecule are in all vaccinated groups. Specific lysis occurred in HAAH- expressed on l-phage (200-300 copies per NPV). These loaded vs. not loaded APCs derived from the same ani- NPVs are immunogenic; producing high-titer anti- mals. Specific lysis of HAAH-loaded rat prostate cancer HAAH polyclonal antibodies in mice despite the fact cells (MLLB cells) was also detected. At effector to target that the HAAH protein is highly conserved between ratios of 25:1, specific lysis ranged from 6-28% (Average = mammalian species. We have further shown that the 17%) dependent on the vaccine type (HAAH-1 vs. HAAH- NPVs inhibit tumor growth and metastasis and extends 3) and the route of delivery (IM vs. ID). survival in mouse models of liver and breast cancer and in a rat model of prostate cancer. It is generally under- Conclusions stood that for a vaccine to provide lasting protective We have previously demonstrated that HAAH-targeted immunity it must also elicit strong cellular immune nanoparticle vaccines are immunogenic and protect responses. Here we demonstrate that these HAAH-tar- against tumor growth and metastasis in vivo and extend geted NPVs can induce antigen specific cytotoxic T cell survival. This work demonstrates that these vaccines also (CTL) responses. elicit a strong humoral response including development of HAAH-specific cytotoxic T-lymphocyte responses. Methods Male Sprague-Dawley rats (N=6/group) were immunized Published: 4 November 2015 with 2.5x10 phage particles displaying either the N-terminal third (HAAH-1l) or the C-terminal third (HAAH-3l) of the HAAH protein. Intramuscular (IM) doi:10.1186/2051-1426-3-S2-P442 immunization of the NPV was compared with intrader- Cite this article as: Lebowitz et al.: A nanoparticle therapeutic vaccine mal (ID) administration using the 3M hMTS device. targeting HAAH stimulates cellular immunity. Journal for ImmunoTherapy of Cancer 2015 3(Suppl 2):P442. Vaccinations occurred on Days 0, 14 and 28 and ani- mals were sacrificed on Day 35. Spleens were harvested + + and CD8 T cells as well as MHC class II antigen pre- senting cells (APC) were isolated using magnetic Panacea Pharmaceuticals, Inc., Gaithersburg, MD, USA © 2015 Lebowitz et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http:// creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/ zero/1.0/) applies to the data made available in this article, unless otherwise stated. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal for ImmunoTherapy of Cancer Springer Journals

A nanoparticle therapeutic vaccine targeting HAAH stimulates cellular immunity

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Publisher
Springer Journals
Copyright
Copyright © 2015 by Lebowitz et al.
Subject
Medicine & Public Health; Oncology
eISSN
2051-1426
DOI
10.1186/2051-1426-3-S2-P442
Publisher site
See Article on Publisher Site

Abstract

Lebowitz et al. Journal for ImmunoTherapy of Cancer 2015, 3(Suppl 2):P442 http://www.immunotherapyofcancer.org/content/3/S2/P442 POSTER PRESENTATION Open Access A nanoparticle therapeutic vaccine targeting HAAH stimulates cellular immunity Michael Lebowitz , Solomon Stewart, Susan Walker, Samindhi Wu, Steven Fuller, Hossein Ghanbari From 30th Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2015) National Harbor, MD, USA. 4-8 November 2015 Background assisted cell sorting (MACS, Milltenyi Biotec). CTL We are evaluating the immunogenicity and efficacy of a responses were measured using a fluorescent assay in nanoparticle vaccine (NPV) targeting the tumor marker which target cells were pre-loaded with 5-(6)-carboxy- human aspartyl (asparaginyl) b-hydroxylase (HAAH). fluorescein diacetate succinimidyl ester (CFSE) and dead HAAH is an embryonic protein that is over-expressed cells were labelled after incubation with effector cells on the surface of cancer cells, is demonstrated to be with 7-amino actinomycin D (7-AAD). responsible for cell proliferation, motility and invasive- ness, processes which can be inhibited by anti-HAAH Results antibodies in vitro. We have developed novel anticancer Antigen specific cytotoxic T cell responses were detected NPVs in which portions of the HAAH molecule are in all vaccinated groups. Specific lysis occurred in HAAH- expressed on l-phage (200-300 copies per NPV). These loaded vs. not loaded APCs derived from the same ani- NPVs are immunogenic; producing high-titer anti- mals. Specific lysis of HAAH-loaded rat prostate cancer HAAH polyclonal antibodies in mice despite the fact cells (MLLB cells) was also detected. At effector to target that the HAAH protein is highly conserved between ratios of 25:1, specific lysis ranged from 6-28% (Average = mammalian species. We have further shown that the 17%) dependent on the vaccine type (HAAH-1 vs. HAAH- NPVs inhibit tumor growth and metastasis and extends 3) and the route of delivery (IM vs. ID). survival in mouse models of liver and breast cancer and in a rat model of prostate cancer. It is generally under- Conclusions stood that for a vaccine to provide lasting protective We have previously demonstrated that HAAH-targeted immunity it must also elicit strong cellular immune nanoparticle vaccines are immunogenic and protect responses. Here we demonstrate that these HAAH-tar- against tumor growth and metastasis in vivo and extend geted NPVs can induce antigen specific cytotoxic T cell survival. This work demonstrates that these vaccines also (CTL) responses. elicit a strong humoral response including development of HAAH-specific cytotoxic T-lymphocyte responses. Methods Male Sprague-Dawley rats (N=6/group) were immunized Published: 4 November 2015 with 2.5x10 phage particles displaying either the N-terminal third (HAAH-1l) or the C-terminal third (HAAH-3l) of the HAAH protein. Intramuscular (IM) doi:10.1186/2051-1426-3-S2-P442 immunization of the NPV was compared with intrader- Cite this article as: Lebowitz et al.: A nanoparticle therapeutic vaccine mal (ID) administration using the 3M hMTS device. targeting HAAH stimulates cellular immunity. Journal for ImmunoTherapy of Cancer 2015 3(Suppl 2):P442. Vaccinations occurred on Days 0, 14 and 28 and ani- mals were sacrificed on Day 35. Spleens were harvested + + and CD8 T cells as well as MHC class II antigen pre- senting cells (APC) were isolated using magnetic Panacea Pharmaceuticals, Inc., Gaithersburg, MD, USA © 2015 Lebowitz et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http:// creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/ zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Journal

Journal for ImmunoTherapy of CancerSpringer Journals

Published: Nov 4, 2015

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