Targeting Nanosystems to Human DCs via Fc Receptor as an Effective Strategy to Deliver Antigen for Immunotherapy

Luis J. Cruz, Felix Rueda, Begona Cordobilla, Lorena Simon, Leticia Hosta Rigau, Fernando Albericio, Joan Caries Domingo

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Dendritic cells (DCs) are increasingly being explored as cellular vaccines for tumor immunotherapy, since they provide an effective system of antigen presentation both in vitro and in vivo. An additional advantage of this cell type is that it is possible to target specific antigens through the activation of receptors, such as FcR (the receptor for the IgG Fc fragment) and TLR (toll-like Receptor). Thus, the uptake capacity of DCs can be improved, thereby increasing antigen presentation. This, in turn, would lead to an enhanced immune response, and, in some instances, the tolerance/anergy of immune effector cells present in cancer patients could be reverted. Here we studied various nanotargeting systems, including liposomes and gold nanopartides of a peptide-based immunotherapeutic vaccine for the treatment of androgen-responsive prostate cancer. Building blocks of the immunogenic peptide consisted of the luteinizing hormone-releasing hormone (LHRH), also known as gonadotropin-releasing hormone (GnRH) peptide (B- and T-cell epitope), in tandem with a T-helper epitope corresponding to the 830-844 region of tetanus toxoid. Three new peptides with several modifications at the N-terminal (palmitoyl, acetyl, and FITC) were synthesized. These peptides also contained a Cys as C-terminal residue to facilitate grafting onto gold nanoparticles. To target different antigen formulations to human DCs, the Fc was activated with a cross-linking spacer to generate a free thiol group and thus facilitate conjugation onto gold nanopartides, liposomes, and peptide. Our results show that gold nanoparticles and liposomes targeted to FcRs of human DCs are effective antigen delivery carriers and induce a strong immune response with respect to nontargeted LHRH-TT-nanopartide conjugates and a superior response to that of naked antigens. In addition, dual labeling using gold and FITC-peptide allowed DC tracking by flow cytometry as well as transmission electron microscopy. Nanoparticles were observed to show a homogeneous distribution throughout the cytoplasm. These results open up a new approach to the development of a novel strategy for cancer vaccines.
Original languageEnglish
JournalMolecular Pharmaceutics
Volume8
Issue number1
Pages (from-to)104-116
Number of pages13
ISSN1543-8384
DOIs
Publication statusPublished - 2011
Externally publishedYes

Keywords

  • Antigens
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Dendritic Cells
  • Flow Cytometry
  • Humans
  • Immunotherapy
  • Liposomes
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Nanoparticles
  • Receptors, Fc
  • Pharmaceutical Science
  • Molecular Medicine
  • Drug Discovery
  • Cancer vaccine
  • Dendritic cells
  • Gold nanoparticles
  • Immunotherapeutic vaccines
  • Peptide vaccines
  • Peptides
  • Targeting
  • acetylated luteinizing hormone releasing hormone tetanus toxoid Fc receptor
  • androgen
  • cancer vaccine
  • cysteine
  • dendritic cell vaccine
  • epitope
  • Fc receptor
  • fluorescein isothiocyanate luteinizing hormone releasing hormone tetanus toxoid Fc receptor
  • gold nanoparticle
  • gonadorelin
  • liposome
  • pamitoyl luteinizing hormone releasing hormone tetanus toxoid Fc receptor
  • peptide vaccine
  • tetanus toxoid
  • thiol derivative
  • thiol group
  • unclassified drug
  • amino terminal sequence
  • article
  • B lymphocyte
  • cancer immunotherapy
  • cell labeling
  • cellular distribution
  • controlled study
  • cross linking
  • cytoplasm
  • dendritic cell
  • drug synthesis
  • drug targeting
  • flow cytometry
  • helper cell
  • hormone response
  • human
  • human cell
  • immune response
  • immunogenicity
  • internalization
  • molecularly targeted therapy
  • priority journal
  • prostate cancer
  • protein synthesis
  • T lymphocyte
  • transmission electron microscopy
  • PHARMACOLOGY
  • HORMONE-RELEASING-HORMONE
  • T-CELL RESPONSES
  • TOTALLY SYNTHETIC VACCINE
  • CLASS-I MHC
  • DENDRITIC CELLS
  • TUMOR-IMMUNITY
  • GOLD NANOPARTICLES
  • GAMMA RECEPTORS
  • PROSTATE-CANCER
  • PEPTIDE MOTIFS
  • gold nanoparticles
  • dendritic cells
  • targeting
  • peptide vaccines
  • immunotherapeutic vaccines
  • Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] human common
  • androgens
  • antigens
  • conjugates
  • epitopes
  • gonadotropin-releasing hormone GnRH 33515-09-2
  • luteinizing hormone-releasing hormone LHRH 9034-40-6
  • 02506, Cytology - Animal
  • 02508, Cytology - Human
  • 10060, Biochemistry studies - General
  • 10064, Biochemistry studies - Proteins, peptides and amino acids
  • 10511, Biophysics - Bioengineering
  • 12512, Pathology - Therapy
  • 15002, Blood - Blood and lymph studies
  • 15004, Blood - Blood cell studies
  • 15506, Urinary system - Pathology
  • 16506, Reproductive system - Pathology
  • 17020, Endocrine - Neuroendocrinology
  • 22002, Pharmacology - General
  • 24003, Neoplasms - Immunology
  • 24004, Neoplasms - Pathology, clinical aspects and systemic effects
  • 34502, Immunology - General and methods
  • 34508, Immunology - Immunopathology, tissue immunology
  • Biomaterials
  • Pharmaceuticals
  • Tumor Biology
  • prostate cancer Prostatic Neoplasms (MeSH) urologic disease, reproductive system disease/male, neoplastic disease
  • drug formulation
  • Pharmacology
  • B-cell immune system, blood and lymphatics
  • dendritic cell immune system
  • T-cell immune system, blood and lymphatics
  • flow cytometry laboratory techniques, histology and cytology techniques
  • immunotherapy therapeutic and prophylactic techniques, clinical techniques
  • transmission electron microscopy laboratory techniques, imaging and microscopy techniques

Fingerprint Dive into the research topics of 'Targeting Nanosystems to Human DCs via Fc Receptor as an Effective Strategy to Deliver Antigen for Immunotherapy'. Together they form a unique fingerprint.

Cite this