title: Polymeric nanoparticles for co-delivery of synthetic long peptide antigen and poly IC as therapeutic cancer vaccine formulation.
abstract: The aim of the current study was to develop a cancer vaccine formulation for treatment of human papillomavirus (HPV)-induced malignancies. Synthetic long peptides (SLPs) derived from HPV16 E6 and E7 oncoproteins have been used for therapeutic vaccination in clinical trials with promising results. In preclinical and clinical studies adjuvants based on mineral oils (such as incomplete Freund's adjuvant (IFA) and Montanide) are used to create a sustained release depot at the injection site. While the depot effect of mineral oils is important for induction of robust immune responses, their administration is accompanied with severe adverse and long lasting side effects. In order to develop an alternative for IFA family of adjuvants, polymeric nanoparticles (NPs) based on hydrophilic polyester (poly(d,l lactic-co-hydroxymethyl glycolic acid) (pLHMGA)) were prepared. These NPs were loaded with a synthetic long peptide (SLP) derived from HPV16 E7 oncoprotein and a toll like receptor 3 (TLR3) ligand (poly IC) by double emulsion solvent evaporation technique. The therapeutic efficacy of the nanoparticulate formulations was compared to that of HPV SLP+poly IC formulated in IFA. Encapsulation of HPV SLP antigen in NPs substantially enhanced the population of HPV-specific CD8+ T cells when combined with poly IC either co-encapsulated with the antigen or in its soluble form. The therapeutic efficacy of NPs containing poly IC in tumor eradication was equivalent to that of the IFA formulation. Importantly, administration of pLHMGA nanoparticles was not associated with adverse effects and therefore these biodegradable nanoparticles are excellent substitutes for IFA in cancer vaccines.
authors: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors: Sima
authors: S
authors: Rahimian
authors: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors: Marieke F
authors: MF
authors: Fransen
authors: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors: Jan Willem
authors: JW
authors: Kleinovink
authors: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors: Jonatan Riis
authors: JR
authors: Christensen
authors: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors: Maryam
authors: M
authors: Amidi
authors: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors: Wim E
authors: WE
authors: Hennink
authors: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: F.A.Ossendorp@lumc.nl.
authors: Ferry
authors: F
authors: Ossendorp
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use; D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002584:Cervix Uteri / Q000821:virology; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D007369:Interferon Inducers / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry; D050725:Papillomavirus E7 Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology / Q000627:therapeutic use; D030361:Papillomavirus Infections / Q000276:immunology / Q000628:therapy*; D011070:Poly I-C / Q000008:administration & dosage* / Q000276:immunology / Q000627:therapeutic use; D011091:Polyesters / Q000737:chemistry; D002583:Uterine Cervical Neoplasms / Q000276:immunology / Q000628:therapy*; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D007369:Interferon Inducers; D050725:Papillomavirus E7 Proteins; D011091:Polyesters; C059731:oncogene protein E7, Human papillomavirus type 16; C576815:poly(lactide-co-hydroxymethyl glycolide); D005620:Freund's Adjuvant; D011070:Poly I-C
keywords: Human papillomavirus (HPV); Incomplete Freund's adjuvant (IFA); Nanoparticles; Poly IC; Synthetic long peptide (SLP); TLR3 ligand; Therapeutic cancer vaccine; pLHMGA