PLGA-Listeriolysin O microspheres: Opening the gate for cytosolic delivery of cancer antigens
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Strategies for cancer protein vaccination largely aim to activate the cellular arm of the immune system against cancer cells. This approach, however, is limited since protein vaccines mostly activate the system’s humoral arm instead. One way to overcome this problem is to enhance the cross-presentation of such proteins by antigen-presenting cells, which may consequently lead to intense cellular response. Here we examined the ability of listeriolysin O (LLO) incorporated into poly-lactic-co-glycolic acid (PLGA) microspheres to modify the cytosolic delivery of low molecular weight peptides and enhance their cross-presentation. PLGA microspheres were produced in a size suitable for uptake by phagocytic cells. The peptide encapsulation and release kinetics were improved by adding NaCl to the preparation. PLGA microspheres loaded with the antigenic peptide and incorporated with LLO were readily up-taken by phagocytic cells, which exhibited an increase in the expression of peptide-MHC-CI complexes on the cell surface. Furthermore, this system enhanced the activation of a specific T hybridoma cell line, thus simulating cytotoxic T cells. These results establish, for the first time, a proof of concept for the use of PLGA microspheres incorporated with a pore-forming agent and the antigen peptide of choice as a unique cancer protein vaccination delivery platform.
KeywordsPLGA LLO Cross-presentation Cancer immunotherapy Microspheres Drug delivery
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Conflict of Interest
The authors declare that they have no conflict of interest.
- O. Benny, M. Duvshani-Eshet, T. Cargioli, L. Bello, A. Bikfalvi, R. S. Carroll and M. Machluf. Clin Cancer Res 11, 2 Pt 1, 768–776 (2005)Google Scholar
- H. J. Byeon, I. Kim, J. S. Choi, E. S. Lee, B. S. Shin, Y. S. Youn, Int J Nanomedicine 10, 739–748 (2015)Google Scholar
- P. Hermann, M. Rubio, T. Nakajima, G. Delespesse, M. Sarfati, J Immunol 161(4), 2011–2018 (1998)Google Scholar
- Jutras, I. and M. Desjardins. Annu Rev Cell Dev Biol 21, 511–527 (2005)Google Scholar
- N. Lassam, G. Jay, J Immunol 143(11), 3792–3797 (1989)Google Scholar
- S. Seveau, Multifaceted activity of listeriolysin O, the cholesterol-dependent cytolysin of Listeria monocytogenes (MACPF/CDC Proteins-Agents of Defence, Attack and Invasion, Springer, 2014), pp. 161–195Google Scholar
- Z. Shen, G. Reznikoff, G. Dranoff, K. L. Rock, J Immunol 158(6), 2723–2730 (1997)Google Scholar
- Tamber, H., P. Johansen, H. P. Merkle and B. Gander. Adv Drug Deliv Rev 57, 3, 357–376 (2005)Google Scholar