Show simple item record

dc.contributor.authorNaito, Masayasu
dc.contributor.authorHainz, Ursula
dc.contributor.authorBurkhardt, Ute E.
dc.contributor.authorFu, Buyin
dc.contributor.authorAhove, Deborah
dc.contributor.authorStevenson, Kristen E.
dc.contributor.authorRajasagi, Mohini
dc.contributor.authorZhu, Baogong
dc.contributor.authorAlonso, Anselmo
dc.contributor.authorWitten, Elizabeth
dc.contributor.authorMatsuoka, Ken-ichi
dc.contributor.authorNeuberg, Donna
dc.contributor.authorDuke-Cohan, Jonathan S.
dc.contributor.authorWu, Cathy Ju-Ying
dc.contributor.authorFreeman, Gordon James
dc.date.accessioned2013-10-16T20:34:14Z
dc.date.issued2012
dc.identifier.citationNaito, Masayasu, Ursula Hainz, Ute E. Burkhardt, Buyin Fu, Deborah Ahove, Kristen E. Stevenson, Mohini Rajasagi, et al. 2012. Cd40l-tri, a novel formulation of recombinant human cd40l that effectively activates b cells. Cancer Immunology, Immunotherapy 62(2): 347-357.en_US
dc.identifier.issn0340-7004en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11179849
dc.description.abstractCD40L has a well-established role in enhancing the immunostimulatory capacity of normal and malignant B cells, but a formulation suitable for clinical use has not been widely available. Like other TNF family members, in vivo and in vitro activity of CD40L requires a homotrimeric configuration, and growing evidence suggests that bioactivity depends on higher-order clustering of CD40. We generated a novel formulation of human recombinant CD40L (CD40L-Tri) in which the CD40L extracellular domain and a trimerization motif are connected by a long flexible peptide linker. We demonstrate that CD40L-Tri significantly expands normal CD19+ B cells by over 20- to 30-fold over 14 days and induces B cells to become highly immunostimulatory antigen-presenting cells (APCs). Consistent with these results, CD40L-Tri-activated B cells could effectively stimulate antigen-specific T responses (against the influenza M1 peptide) from normal volunteers. In addition, CD40L-Tri could induce malignant B cells to become effective APCs, such that tumor-directed immune responses could be probed. Together, our studies demonstrate the potent immune-stimulatory effects of CD40L-Tri on B cells that enable their expansion of antigen-specific human T cells. The potent bioactivity of CD40L-Tri is related to its ability to self-multimerize, which may be facilitated by its long peptide linker. Electronic supplementary material The online version of this article (doi:10.1007/s00262-012-1331-4) contains supplementary material, which is available to authorized users.en_US
dc.language.isoen_USen_US
dc.publisherSpringer-Verlagen_US
dc.relation.isversionofdoi:10.1007/s00262-012-1331-4en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3569584/pdf/en_US
dash.licenseLAA
dc.subjectCD40en_US
dc.subjectCD40Len_US
dc.subjectB lymphocytesen_US
dc.subjectImmunotherapyen_US
dc.subjectAntigen-presenting cellen_US
dc.titleCD40L-Tri, a novel formulation of recombinant human CD40L that effectively activates B cellsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalCancer Immunology, Immunotherapyen_US
dash.depositing.authorFreeman, Gordon James
dc.date.available2013-10-16T20:34:14Z
dc.identifier.doi10.1007/s00262-012-1331-4*
dash.authorsorderedfalse
dash.contributor.affiliatedWu, Catherine
dash.contributor.affiliatedFreeman, Gordon
dash.contributor.affiliatedDuke-Cohan, Jonathan


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record