Human Dendritic Cell Activation Induced by a Permannosylated Dendron Containing an Antigenic GM3-lactone Mimetic

Overview

Journal Beilstein J Org Chem

Specialty Chemistry

Date 2014 Jul 4

PMID 24991284

Authors

Renato Ribeiro-Viana

Elena Bonechi

Javier Rojo

Clara Ballerini

Giuseppina Comito

Barbara Richichi

Cristina Nativi

Affiliations

Soon will be listed here.

Abstract

Vaccination strategies based on dendritic cells (DCs) armed with specific tumor antigens have been widely exploited due the properties of these immune cells in coordinating an innate and adaptive response. Here, we describe the convergent synthesis of the bifunctional multivalent glycodendron 5, which contains nine residues of mannose for DC targeting and one residue of an immunogenic mimetic of a carbohydrate melanoma associated antigen. The immunological assays demonstrated that the glycodendron 5 is able to induce human immature DC activation in terms of a phenotype expression of co-stimulatory molecules expression and MHCII. Furthermore, DCs activated by the glycodendron 5 stimulate T lymphocytes to proliferate in a mixed lymphocytes reaction (MLR).

References

Ribeiro-Viana R, Garcia-Vallejo J, Collado D, Perez-Inestrosa E, Bloem K, van Kooyk Y . BODIPY-labeled DC-SIGN-targeting glycodendrons efficiently internalize and route to lysosomes in human dendritic cells. Biomacromolecules. 2012; 13(10):3209-19. DOI: 10.1021/bm300998c. View

Schmidt S, Nino-Castro A, Schultze J . Regulatory dendritic cells: there is more than just immune activation. Front Immunol. 2012; 3:274. PMC: 3432880. DOI: 10.3389/fimmu.2012.00274. View

Dudziak D, Kamphorst A, Heidkamp G, Buchholz V, Trumpfheller C, Yamazaki S . Differential antigen processing by dendritic cell subsets in vivo. Science. 2007; 315(5808):107-11. DOI: 10.1126/science.1136080. View

Richichi B, Comito G, Cerofolini L, Gabrielli G, Marra A, Moni L . Multivalent presentation of a hydrolytically stable GM(3) lactone mimetic as modulator of melanoma cells motility and adhesion. Bioorg Med Chem. 2013; 21(10):2756-63. DOI: 10.1016/j.bmc.2013.03.021. View

Mansh M . Ipilimumab and cancer immunotherapy: a new hope for advanced stage melanoma. Yale J Biol Med. 2011; 84(4):381-9. PMC: 3238313. View

Geijtenbeek T, Gringhuis S . Signalling through C-type lectin receptors: shaping immune responses. Nat Rev Immunol. 2009; 9(7):465-79. PMC: 7097056. DOI: 10.1038/nri2569. View

Tardif M, Coulombe J, Soulieres D, ROUSSEAU A, Pelletier G . Gangliosides in human uveal melanoma metastatic process. Int J Cancer. 1996; 68(1):97-101. DOI: 10.1002/(SICI)1097-0215(19960927)68:1<97::AID-IJC17>3.0.CO;2-3. View

Arcangeli A, Toma L, Contiero L, Crociani O, Legnani L, Lunghi C . Stable GM3 lactone mimetic raises antibodies specific for the antigens expressed on melanoma cells. Bioconjug Chem. 2010; 21(8):1432-8. DOI: 10.1021/bc900557v. View

Rabinovich G, Gabrilovich D, Sotomayor E . Immunosuppressive strategies that are mediated by tumor cells. Annu Rev Immunol. 2006; 25:267-96. PMC: 2895922. DOI: 10.1146/annurev.immunol.25.022106.141609. View

10.

Mellman I, Coukos G, Dranoff G . Cancer immunotherapy comes of age. Nature. 2011; 480(7378):480-9. PMC: 3967235. DOI: 10.1038/nature10673. View

11.

Heimburg-Molinaro J, Lum M, Vijay G, Jain M, Almogren A, Rittenhouse-Olson K . Cancer vaccines and carbohydrate epitopes. Vaccine. 2011; 29(48):8802-26. PMC: 3208265. DOI: 10.1016/j.vaccine.2011.09.009. View

12.

Figdor C, van Kooyk Y, Adema G . C-type lectin receptors on dendritic cells and Langerhans cells. Nat Rev Immunol. 2002; 2(2):77-84. DOI: 10.1038/nri723. View

13.

Kantoff P, Higano C, Shore N, Berger E, Small E, Penson D . Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010; 363(5):411-22. DOI: 10.1056/NEJMoa1001294. View

14.

Aldinucci A, Rizzetto L, Pieri L, Nosi D, Romagnoli P, Biagioli T . Inhibition of immune synapse by altered dendritic cell actin distribution: a new pathway of mesenchymal stem cell immune regulation. J Immunol. 2010; 185(9):5102-10. DOI: 10.4049/jimmunol.1001332. View

15.

Steinman R, COHN Z . Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med. 1973; 137(5):1142-62. PMC: 2139237. DOI: 10.1084/jem.137.5.1142. View

16.

Igney F, Krammer P . Immune escape of tumors: apoptosis resistance and tumor counterattack. J Leukoc Biol. 2002; 71(6):907-20. View

17.

Higano C, Schellhammer P, Small E, Burch P, Nemunaitis J, Yuh L . Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer. 2009; 115(16):3670-9. DOI: 10.1002/cncr.24429. View

18.

Poggi A, Zocchi M . Mechanisms of tumor escape: role of tumor microenvironment in inducing apoptosis of cytolytic effector cells. Arch Immunol Ther Exp (Warsz). 2006; 54(5):323-33. DOI: 10.1007/s00005-006-0038-7. View

19.

Figdor C, de Vries I, Lesterhuis W, Melief C . Dendritic cell immunotherapy: mapping the way. Nat Med. 2004; 10(5):475-80. DOI: 10.1038/nm1039. View

20.

Toma L, Di Cola E, Ienco A, Legnani L, Lunghi C, Moneti G . Synthesis, conformational studies, binding assessment and liposome insertion of a thioether-bridged mimetic of the antigen GM3 ganglioside lactone. Chembiochem. 2007; 8(14):1646-9. DOI: 10.1002/cbic.200700208. View