Cancer Immunology, Immunotherapy

, Volume 62, Issue 7, pp 1161–1173

Efficient ex vivo induction of T cells with potent anti-tumor activity by protein antigen encapsulated in nanoparticles

  • Rodney A. Rosalia
  • Ana Luisa Silva
  • Marcel Camps
  • Ahmed Allam
  • Wim Jiskoot
  • Sjoerd H. van der Burg
  • Ferry Ossendorp
  • Jaap Oostendorp
Original Article

DOI: 10.1007/s00262-013-1411-0

Cite this article as:
Rosalia, R.A., Silva, A.L., Camps, M. et al. Cancer Immunol Immunother (2013) 62: 1161. doi:10.1007/s00262-013-1411-0

Abstract

Protein antigen (Ag)-based immunotherapies have the advantage to induce T cells with a potentially broad repertoire of specificities. However, soluble protein Ag is generally poorly cross-presented in MHC class I molecules and not efficient in inducing robust cytotoxic CD8+ T cell responses. In the present study, we have applied poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) which strongly improve protein Ag presentation by dendritic cells (DC) in the absence of additional Toll-like receptor ligands or targeting devices. Protein Ag-loaded DC were used as antigen presenting cells to stimulate T cells in vitro and subsequently analyzed in vivo for their anti-tumor effect via adoptive transfer, a treatment strategy widely studied in clinical trials as a therapy against various malignancies. In a direct comparison with soluble protein Ag, we show that DC presentation of protein encapsulated in plain PLGA-NP results in efficient activation of CD4+ and CD8+ T cells as reflected by high numbers of activated CD69+ and CD25+, interferon (IFN)-γ and interleukin (IL)-2-producing T cells. Adoptive transfer of PLGA-NP-activated CD8+ T cells in tumor-bearing mice displayed good in vivo expansion capacity, potent Ag-specific cytotoxicity and IFN-γ cytokine production, resulting in curing mice with established tumors. We conclude that delivery of protein Ag through encapsulation in plain PLGA-NP is a very efficient and simple procedure to stimulate potent anti-tumor T cells.

Keywords

PLGAOVAAg cross-presentationAdoptive immunotherapy

Supplementary material

262_2013_1411_MOESM1_ESM.pdf (53 kb)
Supplementary material 1 (PDF 54 kb)

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Rodney A. Rosalia
    • 1
  • Ana Luisa Silva
    • 2
  • Marcel Camps
    • 3
  • Ahmed Allam
    • 2
  • Wim Jiskoot
    • 2
  • Sjoerd H. van der Burg
    • 4
  • Ferry Ossendorp
    • 3
  • Jaap Oostendorp
    • 1
  1. 1.Department of Clinical Pharmacy and ToxicologyLeiden University Medical CenterLeidenThe Netherlands
  2. 2.Division of Drug Delivery Technology, Leiden/Amsterdam Center for Drug ResearchLeiden UniversityLeidenThe Netherlands
  3. 3.Department of Immunohematology and Blood TransfusionLeiden University Medical CenterLeidenThe Netherlands
  4. 4.Department of Clinical OncologyLeiden University Medical CenterLeidenThe Netherlands