2012
DOI: 10.1007/s00262-012-1381-7
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CD1d-antibody fusion proteins target iNKT cells to the tumor and trigger long-term therapeutic responses

Abstract: Despite the well-established antitumor activity of CD1d-restricted invariant natural killer T lymphocytes (iNKT), their use for cancer therapy has remained challenging. This appears to be due to their strong but short-lived activation followed by long-term anergy after a single administration of the CD1d agonist ligand alpha-galactosylceramide (αGC). As a promising alternative, we obtained sustained mouse iNKT cell responses associated with prolonged antitumor effects through repeated administrations of tumor-… Show more

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Cited by 34 publications
(43 citation statements)
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“…Animal studies and clinical trials using RA and αGalCer independently have shown that these agents are potent therapeutic regimens in the treatment of cancer and immune disorders, as well as for vaccine development (Corgnac et al, 2013; Huang et al, 2013; Iclozan et al, 2013; Ronchi and Falcone, 2008). Previously we have shown that combined treatment of RA and αGalCer decreased breast cancer metastasis growth in a mouse model (Chen and Ross, 2012).…”
Section: Discussionmentioning
confidence: 99%
“…Animal studies and clinical trials using RA and αGalCer independently have shown that these agents are potent therapeutic regimens in the treatment of cancer and immune disorders, as well as for vaccine development (Corgnac et al, 2013; Huang et al, 2013; Iclozan et al, 2013; Ronchi and Falcone, 2008). Previously we have shown that combined treatment of RA and αGalCer decreased breast cancer metastasis growth in a mouse model (Chen and Ross, 2012).…”
Section: Discussionmentioning
confidence: 99%
“…iNKT cells bridge the innate and adaptive arms of the immune system by producing a variety of cytokines very rapidly after stimulation (1,2). In view of their transactivating properties, iNKT cells have been implicated in autoimmunity, viral infection, and tumor immunity (1,4,5). During thymic development, iNKT cells are branched off from conventional T cells at double-positive (DP) stage (6).…”
Section: N Atural Killer T Cells Have Been Well Defined As a Uniquementioning
confidence: 99%
“…In vitro analyses showed that single‐chain variable fragments of these tumor‐specific antibodies in translational fusion with CD1d can effectively target CD1d–αGalCer complexes to tumor cells, enabling their direct recognition by iNKT cells and leading to potent tumor cell lysis. In addition, in vivo studies in tumor‐bearing mice using this approach demonstrated the potential to inhibit tumor growth with activation of a variety of antitumor immune mechanisms that are orchestrated by direct iNKT cell stimulation, including activation of NK cells, release of Th1 cytokines and priming of tumor antigen‐specific cytotoxic CD8 + T cells 115 , 116 , 117 . Cancer‐specific antibodies fused with CD1d/glycolipid complexes also have the advantage of stimulating activation and expansion of iNKT cells while preserving their ability to respond to multiple subsequent stimulations 116 .…”
Section: Antibody Targeting Of Cd1d/glycolipid Complexes To Cancersmentioning
confidence: 99%
“…[115][116][117] Cancer-specific antibodies fused with CD1d/glycolipid complexes also have the advantage of stimulating activation and expansion of iNKT cells while preserving their ability to respond to multiple subsequent stimulations. 116 Efforts in this area are currently directed at identifying the optimal αGalCer analogs for ex vivo loading of targeted CD1d single-chain variable fragment proteins. One recent approach has used photoactivatable derivatives of αGalCer that can be covalently bound to the targeted CD1d, thus stabilizing and extending the half-life of the complex while potentially avoiding unwanted off-target effects.…”
Section: Cell-based Therapy Using αGalcer-pulsed Dcsmentioning
confidence: 99%