Optimizing NKT Cell Ligands As Vaccine adjuvants

Overview

Journal Immunotherapy

Specialties Allergy & Immunology
Pharmacology

Date 2014 Apr 26

PMID 24762075

Citations 42

Authors

Leandro J Carreno

Shalu Sharma Kharkwal

Steven A Porcelli

Affiliations

Soon will be listed here.

Abstract

NKT cells are a subpopulation of T lymphocytes with phenotypic properties of both T and NK cells and a wide range of immune effector properties. In particular, one subset of these cells, known as invariant NKT cells (iNKT cells), has attracted substantial attention because of their ability to be specifically activated by glycolipid antigens presented by a cell surface protein called CD1d. The development of synthetic α-galactosylceramides as a family of powerful glycolipid agonists for iNKT cells has led to approaches for augmenting a wide variety of immune responses, including those involved in vaccination against infections and cancers. Here, we review basic, preclinical and clinical observations supporting approaches to improving immune responses through the use of iNKT cell-activating glycolipids. Results from preclinical animal studies and preliminary clinical studies in humans identify many promising applications for this approach in the development of vaccines and novel immunotherapies.

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References

Gumperz J, Roy C, Makowska A, Lum D, Sugita M, Podrebarac T . Murine CD1d-restricted T cell recognition of cellular lipids. Immunity. 2000; 12(2):211-21. DOI: 10.1016/s1074-7613(00)80174-0. View

Zhou D, Cantu 3rd C, Sagiv Y, Schrantz N, Kulkarni A, Qi X . Editing of CD1d-bound lipid antigens by endosomal lipid transfer proteins. Science. 2003; 303(5657):523-7. PMC: 2918537. DOI: 10.1126/science.1092009. View

GRAY J, Horwitz D . Activated human NK cells can stimulate resting B cells to secrete immunoglobulin. J Immunol. 1995; 154(11):5656-64. View

Im J, Yu K, Illarionov P, LeClair K, Storey J, Kennedy M . Direct measurement of antigen binding properties of CD1 proteins using fluorescent lipid probes. J Biol Chem. 2003; 279(1):299-310. DOI: 10.1074/jbc.M308803200. View

Venkataswamy M, Baena A, Goldberg M, Bricard G, Im J, Chan J . Incorporation of NKT cell-activating glycolipids enhances immunogenicity and vaccine efficacy of Mycobacterium bovis bacillus Calmette-Guerin. J Immunol. 2009; 183(3):1644-56. PMC: 2719834. DOI: 10.4049/jimmunol.0900858. View

Kobayashi E, Motoki K, Uchida T, Fukushima H, Koezuka Y . KRN7000, a novel immunomodulator, and its antitumor activities. Oncol Res. 1995; 7(10-11):529-34. View

Padte N, Li X, Tsuji M, Vasan S . Clinical development of a novel CD1d-binding NKT cell ligand as a vaccine adjuvant. Clin Immunol. 2010; 140(2):142-51. PMC: 4449275. DOI: 10.1016/j.clim.2010.11.009. View

Coquet J, Chakravarti S, Kyparissoudis K, McNab F, Pitt L, McKenzie B . Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4-NK1.1- NKT cell population. Proc Natl Acad Sci U S A. 2008; 105(32):11287-92. PMC: 2516267. DOI: 10.1073/pnas.0801631105. View

Carreno L, Riquelme E, Gonzalez P, Espagnolle N, Riedel C, Valitutti S . T-cell antagonism by short half-life pMHC ligands can be mediated by an efficient trapping of T-cell polarization toward the APC. Proc Natl Acad Sci U S A. 2010; 107(1):210-5. PMC: 2806700. DOI: 10.1073/pnas.0911258107. View

10.

Terabe M, Swann J, Ambrosino E, Sinha P, Takaku S, Hayakawa Y . A nonclassical non-Valpha14Jalpha18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance. J Exp Med. 2005; 202(12):1627-33. PMC: 2212961. DOI: 10.1084/jem.20051381. View

11.

Brigl M, Brenner M . CD1: antigen presentation and T cell function. Annu Rev Immunol. 2004; 22:817-90. DOI: 10.1146/annurev.immunol.22.012703.104608. View

12.

Veldt B, van der Vliet H, von Blomberg B, Van Vlierberghe H, Gerken G, Nishi N . Randomized placebo controlled phase I/II trial of alpha-galactosylceramide for the treatment of chronic hepatitis C. J Hepatol. 2007; 47(3):356-65. DOI: 10.1016/j.jhep.2007.04.018. View

13.

Stober D, Jomantaite I, Schirmbeck R, Reimann J . NKT cells provide help for dendritic cell-dependent priming of MHC class I-restricted CD8+ T cells in vivo. J Immunol. 2003; 170(5):2540-8. DOI: 10.4049/jimmunol.170.5.2540. View

14.

Richter J, Neparidze N, Zhang L, Nair S, Monesmith T, Sundaram R . Clinical regressions and broad immune activation following combination therapy targeting human NKT cells in myeloma. Blood. 2012; 121(3):423-30. PMC: 3548165. DOI: 10.1182/blood-2012-06-435503. View

15.

Lee Y, Holzapfel K, Zhu J, Jameson S, Hogquist K . Steady-state production of IL-4 modulates immunity in mouse strains and is determined by lineage diversity of iNKT cells. Nat Immunol. 2013; 14(11):1146-54. PMC: 3824254. DOI: 10.1038/ni.2731. View

16.

Godfrey D, Rossjohn J . New ways to turn on NKT cells. J Exp Med. 2011; 208(6):1121-5. PMC: 3173239. DOI: 10.1084/jem.20110983. View

17.

Kitamura H, Ohta A, Sekimoto M, Sato M, Iwakabe K, Nakui M . alpha-galactosylceramide induces early B-cell activation through IL-4 production by NKT cells. Cell Immunol. 2000; 199(1):37-42. DOI: 10.1006/cimm.1999.1602. View

18.

Stetson D, Mohrs M, Reinhardt R, Baron J, Wang Z, Gapin L . Constitutive cytokine mRNAs mark natural killer (NK) and NK T cells poised for rapid effector function. J Exp Med. 2003; 198(7):1069-76. PMC: 2194220. DOI: 10.1084/jem.20030630. View

19.

Bricard G, Porcelli S . Antigen presentation by CD1 molecules and the generation of lipid-specific T cell immunity. Cell Mol Life Sci. 2007; 64(14):1824-40. PMC: 11136151. DOI: 10.1007/s00018-007-7007-0. View

20.

Speak A, Salio M, Neville D, Fontaine J, Priestman D, Platt N . Implications for invariant natural killer T cell ligands due to the restricted presence of isoglobotrihexosylceramide in mammals. Proc Natl Acad Sci U S A. 2007; 104(14):5971-6. PMC: 1851601. DOI: 10.1073/pnas.0607285104. View