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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
authors.affiliation: Moores UCSD Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA, 92093-0815, USA. dfutalan@uci.edu.
authors.forename: Diahnn F
authors.initials: DF
authors.lastname: Campbell
authors.affiliation: Moores UCSD Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA, 92093-0815, USA. rksaenz@stanford.edu.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Saenz
authors.affiliation: Moores UCSD Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA, 92093-0815, USA. isummit@genoptix.com.
authors.forename: Ila S
authors.initials: IS
authors.lastname: Bharati
authors.affiliation: Moores UCSD Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA, 92093-0815, USA. dseible@gmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Seible
authors.affiliation: Department of Nanoengineering, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA, 92093-0815, USA. zhang@ucsd.edu.
authors.forename: Liangfang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Bioengineering, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA, 92093-0815, USA. sesener@ucsd.edu.
authors.forename: Sadik
authors.initials: S
authors.lastname: Esener
authors.affiliation: Moores UCSD Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA, 92093-0815, USA. bmessmer@ucsd.edu.
authors.forename: Bradley
authors.initials: B
authors.lastname: Messmer
authors.affiliation: Division of Molecular Virology, Department of Clinical and Experimental Medicine, Sandbäcksgatan 7, Linköping University, 581 83, Linköping, Sweden. marie.larsson@liu.se.
authors.forename: Marie
authors.initials: M
authors.lastname: Larsson
authors.affiliation: Moores UCSD Cancer Center, University of California San Diego, 3855 Health Sciences Drive, La Jolla, CA, 92093-0815, USA. dmessmer@inceptionsci.com.|Inception Sciences, 5871 Oberlin Drive, San Diego, CA, 92121, USA. dmessmer@inceptionsci.com.
authors.forename: Davorka
authors.initials: D
authors.lastname: Messmer
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001943:Breast Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D019496:Cancer Vaccines / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007114:Immunization; D056747:Immunomodulation; D019344:Lactic Acid / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D053758:Nanoparticles / Q000008:administration & dosage*; D010455:Peptides / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D047368:Tumor Burden / Q000235:genetics / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D019344:Lactic Acid; D010455:Peptides; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D018719:Erb-b2 Receptor Tyrosine Kinases