Introduction of functional chimeric E/L-selectin by RNA electroporation to target dendritic cells from blood to lymph nodes

Dorrie J, Schaft N, Muller I, Wellner V, Schunder T, Hanig J, Oostingh GJ, Schon MP, Robert C, Kampgen E, Schuler G
Cancer Immunol Immunother. 57 (4)467-77, 2008

BACKGROUND: Inefficient migration of dendritic cells (DC) to regional lymph nodes (LN) upon intracutaneous injection is a major obstacle for effective DC vaccination. Intravenous vaccination is unfavorable, because DC cannot migrate directly from the blood into LN. METHODS: To enable human monocyte-derived (mo)DC to enter LN directly from the blood, we manipulated them by RNA electroporation to express a human chimeric E/L-selectin (CD62E/CD62L) protein, which binds to peripheral node addressin expressed on high endothelial venules. RESULTS: Transfection efficiency exceeded 95%, and high E/L-selectin surface expression was detected for >48 h. E/L-selectin RNA-transfected DC displayed an identical mature DC phenotype as mock-transfected DC. Furthermore, E/L-selectin-transfected DC maintained their normal CCR7-mediated migration capacity, and their ability to prime and expand functional cytotoxic T cells recognizing MelanA. Most importantly, E/L-selectin-RNA-transfected DC gained the capability to attach to and roll on sialyl-Lewis(X) in vitro. OUTLOOK: The presented strategy can be readily translated into the clinic, as it involves no stable genetic manipulation or viral transformation, and allows targeting of a large number of LN.

URL: http://www.springerlink.com/content/u4126m3360226m55/

Pub Med: http://www.ncbi.nlm.nih.gov/pubmed/17768622

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