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Polymeric nanoparticles for co-delivery of synthetic long peptide antigen and poly IC as therapeutic cancer vaccine formulation.
- Source :
-
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2015 Apr 10; Vol. 203, pp. 16-22. Date of Electronic Publication: 2015 Feb 07. - Publication Year :
- 2015
-
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.<br /> (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Subjects :
- Adjuvants, Immunologic administration & dosage
Adjuvants, Immunologic therapeutic use
Amino Acid Sequence
Animals
CD8-Positive T-Lymphocytes immunology
Cancer Vaccines chemistry
Cancer Vaccines immunology
Cancer Vaccines therapeutic use
Cell Line, Tumor
Cervix Uteri virology
Female
Freund's Adjuvant administration & dosage
Freund's Adjuvant immunology
Freund's Adjuvant therapeutic use
Humans
Interferon Inducers immunology
Interferon Inducers therapeutic use
Mice, Inbred C57BL
Molecular Sequence Data
Nanoparticles chemistry
Papillomavirus E7 Proteins chemistry
Papillomavirus E7 Proteins immunology
Papillomavirus E7 Proteins therapeutic use
Papillomavirus Infections immunology
Poly I-C immunology
Poly I-C therapeutic use
Polyesters chemistry
Uterine Cervical Neoplasms immunology
Vaccination
Cancer Vaccines administration & dosage
Human papillomavirus 16 immunology
Interferon Inducers administration & dosage
Papillomavirus E7 Proteins administration & dosage
Papillomavirus Infections therapy
Poly I-C administration & dosage
Uterine Cervical Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4995
- Volume :
- 203
- Database :
- MEDLINE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Publication Type :
- Academic Journal
- Accession number :
- 25660830
- Full Text :
- https://doi.org/10.1016/j.jconrel.2015.02.006