Protein Transduction Domain Mimics Facilitate Rapid Antigen Delivery into Monocytes

Coralie M. Backlund, Ladan Parhamifar, Lisa Minter, Gregory N. Tew*, Thomas L. Andresen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Delivering peptides and proteins with intracellular function represents a promising avenue for therapeutics, but remains a challenge due to the selective permeability of the plasma membrane. The successful delivery of cytosolically active proteins would enable many opportunities, including improved vaccine development through major histocompatibility complex (MHC) class I antigen display. Extended research using cell-penetrating peptides (CPPs) has aimed to facilitate intracellular delivery of exogenous proteins with some success. A new class of polymer-based mimics termed protein transduction domain mimics (PTDMs), which maintain the positive charge and amphiphilic nature displayed by many CPPs, was developed using a poly-norbornene-based backbone. Herein, we use a previously characterized PTDM to investigate delivery of the model antigen SIINFEKL into leukocytes. Peptide delivery into over 90% of CD14+ monocytes was detected in less than 15 min with nominal inflammatory cytokine response and high cell viability. The co-delivery of a TLR9 agonist and antigen using the PTDM into antigen presenting cells in vitro showed presentation of SIINFEKL in association with MHC class I molecules, in addition to upregulation of classical differentiation markers revealing the ability of the PTDM to successfully deliver cargo intracellularly and show application in the field of immunotherapy.
Original languageEnglish
JournalMolecular Pharmaceutics
Volume16
Issue number6
Pages (from-to)2462-2469
ISSN1543-8384
DOIs
Publication statusPublished - 2019

Cite this

Backlund, Coralie M. ; Parhamifar, Ladan ; Minter, Lisa ; Tew, Gregory N. ; Andresen, Thomas L. / Protein Transduction Domain Mimics Facilitate Rapid Antigen Delivery into Monocytes. In: Molecular Pharmaceutics. 2019 ; Vol. 16, No. 6. pp. 2462-2469.
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title = "Protein Transduction Domain Mimics Facilitate Rapid Antigen Delivery into Monocytes",
abstract = "Delivering peptides and proteins with intracellular function represents a promising avenue for therapeutics, but remains a challenge due to the selective permeability of the plasma membrane. The successful delivery of cytosolically active proteins would enable many opportunities, including improved vaccine development through major histocompatibility complex (MHC) class I antigen display. Extended research using cell-penetrating peptides (CPPs) has aimed to facilitate intracellular delivery of exogenous proteins with some success. A new class of polymer-based mimics termed protein transduction domain mimics (PTDMs), which maintain the positive charge and amphiphilic nature displayed by many CPPs, was developed using a poly-norbornene-based backbone. Herein, we use a previously characterized PTDM to investigate delivery of the model antigen SIINFEKL into leukocytes. Peptide delivery into over 90{\%} of CD14+ monocytes was detected in less than 15 min with nominal inflammatory cytokine response and high cell viability. The co-delivery of a TLR9 agonist and antigen using the PTDM into antigen presenting cells in vitro showed presentation of SIINFEKL in association with MHC class I molecules, in addition to upregulation of classical differentiation markers revealing the ability of the PTDM to successfully deliver cargo intracellularly and show application in the field of immunotherapy.",
author = "Backlund, {Coralie M.} and Ladan Parhamifar and Lisa Minter and Tew, {Gregory N.} and Andresen, {Thomas L.}",
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Protein Transduction Domain Mimics Facilitate Rapid Antigen Delivery into Monocytes. / Backlund, Coralie M.; Parhamifar, Ladan; Minter, Lisa; Tew, Gregory N.; Andresen, Thomas L.

In: Molecular Pharmaceutics, Vol. 16, No. 6, 2019, p. 2462-2469.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Protein Transduction Domain Mimics Facilitate Rapid Antigen Delivery into Monocytes

AU - Backlund, Coralie M.

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AU - Minter, Lisa

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AU - Andresen, Thomas L.

PY - 2019

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AB - Delivering peptides and proteins with intracellular function represents a promising avenue for therapeutics, but remains a challenge due to the selective permeability of the plasma membrane. The successful delivery of cytosolically active proteins would enable many opportunities, including improved vaccine development through major histocompatibility complex (MHC) class I antigen display. Extended research using cell-penetrating peptides (CPPs) has aimed to facilitate intracellular delivery of exogenous proteins with some success. A new class of polymer-based mimics termed protein transduction domain mimics (PTDMs), which maintain the positive charge and amphiphilic nature displayed by many CPPs, was developed using a poly-norbornene-based backbone. Herein, we use a previously characterized PTDM to investigate delivery of the model antigen SIINFEKL into leukocytes. Peptide delivery into over 90% of CD14+ monocytes was detected in less than 15 min with nominal inflammatory cytokine response and high cell viability. The co-delivery of a TLR9 agonist and antigen using the PTDM into antigen presenting cells in vitro showed presentation of SIINFEKL in association with MHC class I molecules, in addition to upregulation of classical differentiation markers revealing the ability of the PTDM to successfully deliver cargo intracellularly and show application in the field of immunotherapy.

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