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CD40-targeted dendritic cell delivery of PLGA-nanoparticle vaccines induce potent anti-tumor responses

Paper ID Volume ID Publish Year Pages File Format Full-Text
5760 426 2015 10 PDF Available
Title
CD40-targeted dendritic cell delivery of PLGA-nanoparticle vaccines induce potent anti-tumor responses
Abstract

Dendritic cells (DC) play a prominent role in the priming of CD8+ T cells. Vaccination is a promising treatment to boost tumor-specific CD8+ T cells which is crucially dependent on adequate delivery of the vaccine to DC. Upon subcutaneous (s.c.) injection, only a small fraction of the vaccine is delivered to DC whereas the majority is cleared by the body or engulfed by other immune cells.To overcome this, we studied vaccine delivery to DC via CD40-targeting using a multi-compound particulate vaccine with the aim to induce potent CD8+ T cell responses. To this end, biodegradable poly(lactic-co-glycolic acid) nanoparticles (NP) were formulated encapsulating a protein Ag, Pam3CSK4 and Poly(I:C) and coated with an agonistic αCD40-mAb (NP-CD40). Targeting NP to CD40 led to very efficient and selective delivery to DC in vivo upon s.c. injection and improved priming of CD8+ T cells against two independent tumor associated Ag. Therapeutic application of NP-CD40 enhanced tumor control and prolonged survival of tumor-bearing mice.We conclude that CD40-mediated delivery to DC of NP-vaccines, co-encapsulating Ag and adjuvants, efficiently drives specific T cell responses, and therefore, is an attractive method to improve the efficacy of protein based cancer vaccines undergoing clinical testing in the clinic.

Keywords
PLGA nanoparticles; Vaccine; DC; Targeting; TLR ligands; CD40PLGA, poly-(lactic-co-glycolic-acid); NP, nanoparticles; TLRL, TLR ligands
First Page Preview
CD40-targeted dendritic cell delivery of PLGA-nanoparticle vaccines induce potent anti-tumor responses
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 40, February 2015, Pages 88–97
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering