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Engrafting Costimulator Molecules onto Tumor Cell Surfaces with Chelator Lipids: A Potentially Convenient Approach in Cancer Vaccine Development

Van Broekhoven, Christina; Vassiliou, G; Altin, Joseph; Parish, Christopher

Description

The genetic modification of cells to develop cell-based vaccines and to modulate immune responses in vivo can be risky and inconvenient to perform in clinical situations. A novel chelator lipid, nitrilotriacetic acid di- tetradecylamine (NTA-DTDA) that, via the NTA group has high affinity for 6His peptide, was used to directly anchor recombinant forms of T cell costimulatory molecules containing a C-terminal 6-His sequence onto tumor cell surfaces. Initial experiments using murine P815 tumor...[Show more]

dc.contributor.authorVan Broekhoven, Christina
dc.contributor.authorVassiliou, G
dc.contributor.authorAltin, Joseph
dc.contributor.authorParish, Christopher
dc.date.accessioned2015-12-13T23:18:43Z
dc.identifier.issn0022-1767
dc.identifier.urihttp://hdl.handle.net/1885/90314
dc.description.abstractThe genetic modification of cells to develop cell-based vaccines and to modulate immune responses in vivo can be risky and inconvenient to perform in clinical situations. A novel chelator lipid, nitrilotriacetic acid di- tetradecylamine (NTA-DTDA) that, via the NTA group has high affinity for 6His peptide, was used to directly anchor recombinant forms of T cell costimulatory molecules containing a C-terminal 6-His sequence onto tumor cell surfaces. Initial experiments using murine P815 tumor cells established the optimum conditions for incorporating NTA-DTDA onto the membranes of cells. P815 cells with incorporated NTA-DTDA bound hexahistidine-(6His)- tagged forms of the extracellular domains of murine B7.1 and CD40 (B7.1-6H and CD40-6H) at very high levels (fluorescence 200-300-fold above background), and both proteins could be anchored onto the cells simultaneously. Significant loss of the anchored or 'engrafted' protein occurred through membrane internalization following culture of the cells under physiological conditions, but P815 cells with engrafted B7.1-6H and/or CD40-6H stimulated the proliferation of allogenic and syngeneic splenic T cells in vitro, and generated cytotoxic T cells when used as vaccines in syngeneic animals. Furthermore, the immunization of syngeneic mice with P815 cells engrafted with B7.1-6H or with B7.1-6H and CD40-6H induced protection against challenge with the native P815 tumor. The results indicate that the use of chelator lipids like NTD-DTDA to engraft costimulatory and/or other molecules onto cell membranes could provide a convenient alternative to transfection in the development of cell-based vaccines and for modulation of immune function.
dc.publisherAmerican Association of Immunologists
dc.sourceJournal of Immunology
dc.subjectKeywords: B7 antigen; cancer vaccine; CD40 antigen; chelating agent; immunostimulating agent; nitrilotriacetic acid ditetradecylamine; unclassified drug; animal cell; animal experiment; animal model; article; carboxy terminal sequence; cell membrane; cell protectio
dc.titleEngrafting Costimulator Molecules onto Tumor Cell Surfaces with Chelator Lipids: A Potentially Convenient Approach in Cancer Vaccine Development
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume164
dc.date.issued2000
local.identifier.absfor111299 - Oncology and Carcinogenesis not elsewhere classified
local.identifier.absfor110709 - Tumour Immunology
local.identifier.ariespublicationMigratedxPub20641
local.type.statusPublished Version
local.contributor.affiliationVan Broekhoven, Christina, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationParish, Christopher, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationVassiliou, G, University of Ottawa
local.contributor.affiliationAltin, Joseph, College of Medicine, Biology and Environment, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.startpage2433
local.bibliographicCitation.lastpage2443
dc.date.updated2015-12-12T08:58:06Z
local.identifier.scopusID2-s2.0-0034162536
CollectionsANU Research Publications

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