Immobilized cytokines as biomaterials for manufacturing immune cell based vaccines.
Manufacturing of bioactive cell culture substrates represents a major challenge for the development of cell therapy for tissue repair and immune treatment of cancers, infectious diseases, or immunodeficiencies. In this context, we evaluated the capacity of several differentiation factors, including Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) and Macrophage Colony Stimulating Factor (M-CSF), to drive differentiation of primary cell cultures, once immobilized on surfaces. We show that covalently immobilized signal factors fully retain their biological properties and efficiently promote differentiation of mouse and/or human precursor cells leading to the production of dendritic cells and macrophages. For GM-CSF, we also show that the efficiency of receptor signaling is comparable using either soluble or tethered molecules. Such artificial bioactive interfaces are suitable for the development and automated production of cell-based vaccines and therapies.
Leclerc
Claude
C
Institut Pasteur, Unité de Régulation Immunitaire et Vaccinologie, F-75015 Paris, France.
Brose
Claudia
C
Nouzé
Clémence
C
Leonard
Fransisca
F
Majlessi
Laleh
L
Becker
Sybille
S
von Briesen
Hagen
H
Lo-Man
Richard
R
D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010766:Phosphorylation / Q000187:drug effects; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014614:Vaccines, Synthetic / Q000096:biosynthesis*
D001672:Biocompatible Materials; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D050799:STAT5 Transcription Factor; D014614:Vaccines, Synthetic; D016173:Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor