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.

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

doi:10.1186/s13058-015-0552-9

Abstract

IntroductionCancer 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.MethodIn this study, Hp91 was tested as part of a therapeutic vaccine against human epidermal growth factor receptor 2 (HER2)-positive breast cancer.ResultsFree 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.ConclusionsTaken 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-015-0552-9) contains supplementary material, which is available to authorized users.

Highlights

Cancer vaccines have the potential to induce curative anti-tumor immune responses and better adjuvants may improve vaccine efficacy
The immunostimulatory peptide Hp91, which is derived from the endogenous protein high-mobility group box protein 1 (HMGB1), activates dendritic cells (DCs) [13] and primes antigen-specific cytotoxic T lymphocyte (CTL) responses in vitro [13] and in vivo [14]
Our results demonstrate that the delivery of the immunostimulatory peptide Hp91 inside the PLGA-NPs enhances the efficacy of this breast cancer vaccine

Summary

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. Vaccines need to stimulate DCs to induce potent immune responses. The immunostimulatory peptide Hp91, which is derived from the endogenous protein high-mobility group box protein 1 (HMGB1), activates DCs [13] and primes antigen-specific cytotoxic T lymphocyte (CTL) responses in vitro [13] and in vivo [14]. Hp91 packaged inside of PLGA-NPs is more potent in activating DCs as compared to free peptide [15]. Our results demonstrate that the delivery of the immunostimulatory peptide Hp91 inside the PLGA-NPs enhances the efficacy of this breast cancer vaccine

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