Skip to main content
Top
Published in: Breast Cancer Research 1/2015

Open Access 01-12-2015 | Research article

Enhanced anti-tumor immune responses and delay of tumor development in human epidermal growth factor receptor 2 mice immunized with an immunostimulatory peptide in poly(D,L-lactic-co-glycolic) acid nanoparticles

Authors: Diahnn F Campbell, Rebecca Saenz, Ila S Bharati, Daniel Seible, Liangfang Zhang, Sadik Esener, Bradley Messmer, Marie Larsson, Davorka Messmer

Published in: Breast Cancer Research | Issue 1/2015

Login to get access

Abstract

Introduction

Cancer vaccines have the potential to induce curative anti-tumor immune responses and better adjuvants may improve vaccine efficacy. We have previously shown that Hp91, a peptide derived from the B box domain in high-mobility group box protein 1 (HMGB1), acts as a potent immune adjuvant.

Method

In this study, Hp91 was tested as part of a therapeutic vaccine against human epidermal growth factor receptor 2 (HER2)-positive breast cancer.

Results

Free peptide did not significantly augment immune responses but, when delivered in poly(D,L-lactic-co-glycolic) acid nanoparticles (PLGA-NPs), robust activation of dendritic cells (DCs) and increased activation of HER2-specific T cells was observed in vitro. Vaccination of HER2/neu transgenic mice, a mouse breast cancer model that closely mimics the immune modulation and tolerance in some breast cancer patients, with Hp91-loaded PLGA-NPs enhanced the activation of HER2-specific cytotoxic T lymphocyte (CTL) responses, delayed tumor development, and prolonged survival.

Conclusions

Taken together these findings demonstrate that the delivery of the immunostimulatory peptide Hp91 inside PLGA-NPs enhances the potency of the peptide and efficacy of a breast cancer vaccine.
Appendix
Available only for authorised users
Literature
1.
go back to reference Fournier P, Schirrmacher V. Randomized clinical studies of anti-tumor vaccination: state of the art in 2008. Expert Rev Vaccines. 2009;8:51–66.CrossRefPubMed Fournier P, Schirrmacher V. Randomized clinical studies of anti-tumor vaccination: state of the art in 2008. Expert Rev Vaccines. 2009;8:51–66.CrossRefPubMed
2.
3.
go back to reference Network TCGA. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490:61–70.CrossRef Network TCGA. Comprehensive molecular portraits of human breast tumours. Nature. 2012;490:61–70.CrossRef
4.
go back to reference Audran R, Peter K, Dannull J, Men Y, Scandella E, Groettrup M, et al. Encapsulation of peptides in biodegradable microspheres prolongs their MHC class-I presentation by dendritic cells and macrophages in vitro. Vaccine. 2003;21:1250–5.CrossRefPubMed Audran R, Peter K, Dannull J, Men Y, Scandella E, Groettrup M, et al. Encapsulation of peptides in biodegradable microspheres prolongs their MHC class-I presentation by dendritic cells and macrophages in vitro. Vaccine. 2003;21:1250–5.CrossRefPubMed
5.
go back to reference Uto T, Wang X, Sato K, Haraguchi M, Akagi T, Akashi M, et al. Targeting of antigen to dendritic cells with poly(gamma-glutamic acid) nanoparticles induces antigen-specific humoral and cellular immunity. J Immunol. 2007;178:2979–86.CrossRefPubMed Uto T, Wang X, Sato K, Haraguchi M, Akagi T, Akashi M, et al. Targeting of antigen to dendritic cells with poly(gamma-glutamic acid) nanoparticles induces antigen-specific humoral and cellular immunity. J Immunol. 2007;178:2979–86.CrossRefPubMed
6.
go back to reference Diwan M, Tafaghodi M, Samuel J. Enhancement of immune responses by co-delivery of a CpG oligodeoxynucleotide and tetanus toxoid in biodegradable nanospheres. J Control Release. 2002;85:247–62.CrossRefPubMed Diwan M, Tafaghodi M, Samuel J. Enhancement of immune responses by co-delivery of a CpG oligodeoxynucleotide and tetanus toxoid in biodegradable nanospheres. J Control Release. 2002;85:247–62.CrossRefPubMed
7.
go back to reference Lemoine D, Preat V. Polymeric nanoparticles as delivery system for influenza virus glycoproteins. J Control Release. 1998;54:15–27.CrossRefPubMed Lemoine D, Preat V. Polymeric nanoparticles as delivery system for influenza virus glycoproteins. J Control Release. 1998;54:15–27.CrossRefPubMed
8.
go back to reference Fonseca C, Simoes S, Gaspar R. Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity. J Control Release. 2002;83:273–86.CrossRefPubMed Fonseca C, Simoes S, Gaspar R. Paclitaxel-loaded PLGA nanoparticles: preparation, physicochemical characterization and in vitro anti-tumoral activity. J Control Release. 2002;83:273–86.CrossRefPubMed
9.
go back to reference des Rieux A, Fievez V, Garinot M, Schneider YJ, Preat V. Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach. J Control Release. 2006; 116:1–27. des Rieux A, Fievez V, Garinot M, Schneider YJ, Preat V. Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach. J Control Release. 2006; 116:1–27.
10.
go back to reference Lee SY, Oh JH, Kim JC, Kim YH, Kim SH, Choi JW. In vivo conjunctival reconstruction using modified PLGA grafts for decreased scar formation and contraction. Biomaterials. 2003;24:5049–59.CrossRefPubMed Lee SY, Oh JH, Kim JC, Kim YH, Kim SH, Choi JW. In vivo conjunctival reconstruction using modified PLGA grafts for decreased scar formation and contraction. Biomaterials. 2003;24:5049–59.CrossRefPubMed
11.
go back to reference Ayalasomayajula SP, Kompella UB. Subconjunctivally administered celecoxib-PLGA microparticles sustain retinal drug levels and alleviate diabetes-induced oxidative stress in a rat model. Eur J Pharmacol. 2005;511:191–8.CrossRefPubMed Ayalasomayajula SP, Kompella UB. Subconjunctivally administered celecoxib-PLGA microparticles sustain retinal drug levels and alleviate diabetes-induced oxidative stress in a rat model. Eur J Pharmacol. 2005;511:191–8.CrossRefPubMed
12.
13.
go back to reference Telusma G, Datta S, Mihajlov I, Ma W, Li J, Yang H, et al. Dendritic cell activating peptides induce distinct cytokine profiles. Int Immunol. 2006;18:1563–73.CrossRefPubMed Telusma G, Datta S, Mihajlov I, Ma W, Li J, Yang H, et al. Dendritic cell activating peptides induce distinct cytokine profiles. Int Immunol. 2006;18:1563–73.CrossRefPubMed
14.
go back to reference Saenz R, Souza CD, Huang CT, Larsson M, Esener S, Messmer D. HMGB1-derived peptide acts as adjuvant inducing immune responses to peptide and protein antigen. Vaccine. 2010;28:7556–62.CrossRefPubMedPubMedCentral Saenz R, Souza CD, Huang CT, Larsson M, Esener S, Messmer D. HMGB1-derived peptide acts as adjuvant inducing immune responses to peptide and protein antigen. Vaccine. 2010;28:7556–62.CrossRefPubMedPubMedCentral
15.
go back to reference Clawson C, Huang CT, Futalan D, Seible DM, Saenz R, Larsson M, et al. Delivery of a peptide via poly(D, L-lactic-co-glycolic) acid nanoparticles enhances its dendritic cell-stimulatory capacity. Nanomedicine. 2010;6:651–61.PubMedPubMedCentral Clawson C, Huang CT, Futalan D, Seible DM, Saenz R, Larsson M, et al. Delivery of a peptide via poly(D, L-lactic-co-glycolic) acid nanoparticles enhances its dendritic cell-stimulatory capacity. Nanomedicine. 2010;6:651–61.PubMedPubMedCentral
16.
go back to reference Song H, Shahverdi K, Huso DL, Wang Y, Fox JJ, Hobbs RF, et al. An immunotolerant HER-2/neu transgenic mouse model of metastatic breast cancer. Clin Cancer Res. 2008;14:6116–24.CrossRefPubMedPubMedCentral Song H, Shahverdi K, Huso DL, Wang Y, Fox JJ, Hobbs RF, et al. An immunotolerant HER-2/neu transgenic mouse model of metastatic breast cancer. Clin Cancer Res. 2008;14:6116–24.CrossRefPubMedPubMedCentral
17.
go back to reference Inaba K, Inaba M, Romani N, Aya H, Deguchi M, Ikehara S, et al. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med. 1992;176:1693–702.CrossRefPubMed Inaba K, Inaba M, Romani N, Aya H, Deguchi M, Ikehara S, et al. Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor. J Exp Med. 1992;176:1693–702.CrossRefPubMed
18.
go back to reference Messmer D, Yang H, Telusma G, Knoll F, Li J, Messmer B, et al. High mobility group box protein 1: an endogenous signal for dendritic cell maturation and Th1 polarization. J Immunol. 2004;173:307–13.CrossRefPubMed Messmer D, Yang H, Telusma G, Knoll F, Li J, Messmer B, et al. High mobility group box protein 1: an endogenous signal for dendritic cell maturation and Th1 polarization. J Immunol. 2004;173:307–13.CrossRefPubMed
19.
go back to reference Uto T, Akagi T, Yoshinaga K, Toyama M, Akashi M, Baba M. The induction of innate and adaptive immunity by biodegradable poly(gamma-glutamic acid) nanoparticles via a TLR4 and MyD88 signaling pathway. Biomaterials. 2011;32:5206–12.CrossRefPubMed Uto T, Akagi T, Yoshinaga K, Toyama M, Akashi M, Baba M. The induction of innate and adaptive immunity by biodegradable poly(gamma-glutamic acid) nanoparticles via a TLR4 and MyD88 signaling pathway. Biomaterials. 2011;32:5206–12.CrossRefPubMed
Metadata
Title
Enhanced anti-tumor immune responses and delay of tumor development in human epidermal growth factor receptor 2 mice immunized with an immunostimulatory peptide in poly(D,L-lactic-co-glycolic) acid nanoparticles
Authors
Diahnn F Campbell
Rebecca Saenz
Ila S Bharati
Daniel Seible
Liangfang Zhang
Sadik Esener
Bradley Messmer
Marie Larsson
Davorka Messmer
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2015
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-015-0552-9

Other articles of this Issue 1/2015

Breast Cancer Research 1/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine