In Vivo Targeting of Dendritic Cells with Artificial Adjuvant Vector Cells (aAVC) as a Novel Cancer Immunotherapy
An ideal cancer vaccine would inhibit tumor cells by inducing both innate and adaptive immunity, allowing for specific and long-term cancer immunosurveillance.
Dendritic cells (DCs) and invariant natural killer T (iNKT) cells are excellent targets for this type of tumor immunotherapy development. DCs are innate immune cells that initiate and shape adaptive immunity through naïve T cell priming and chemokine/cytokine secretion, while iNKT cells induce the maturation of endogenous DCs in situ, thereby linking innate and adaptive immunity.
Our laboratory has established a unique method of targeting in vivo DCs using a cell vector system comprised of glycolipid-loaded, mRNA-transfected allogeneic cells. These cells provide iNKT cell activation, DC maturation, and tumor-specific T cell immunity. This unique tool could prove clinically beneficial in the development of immunotherapies against malignant and infectious diseases.
KeywordsiNKT cells Adjuvant effects Dendritic cells α-Galactosylceramide Cross-presentation
- Chang DH, Osman K, Connolly J, Kukreja A, Krasovsky J, Pack M, Hutchinson A, Geller M, Liu N, Annable R, Shay J, Kirchhoff K, Nishi N, Ando Y, Hayashi K, Hassoun H, Steinman RM, Dhodapkar MV (2005) Sustained expansion of NKT cells and antigen-specific T cells after injection of α-galactosyl-ceramide loaded mature dendritic cells in cancer patients. J Exp Med 201(9):1503–1517CrossRefPubMedCentralPubMedGoogle Scholar
- Dondji B, Deak E, Goldsmith-Pestana K, Perez-Jimenez E, Esteban M, Miyake S, Yamamura T, McMahon-Pratt D (2008) Intradermal NKT cell activation during DNA priming in heterologous prime-boost vaccination enhances T cell responses and protection against Leishmania. Eur J Immunol 38(3):706–719CrossRefPubMedCentralPubMedGoogle Scholar
- Fujii S, Shimizu K, Smith C, Bonifaz L, Steinman RM (2003) Activation of natural killer T cells by α-galactosylceramide rapidly induces the full maturation of dendritic cells in vivo and thereby acts as an adjuvant for combined CD4 and CD8 T cell immunity to a co-administered protein. J Exp Med 198(2):267–279CrossRefPubMedCentralPubMedGoogle Scholar
- Guillonneau C, Mintern JD, Hubert FX, Hurt AC, Besra GS, Porcelli S, Barr IG, Doherty PC, Godfrey DI, Turner SJ (2009) Combined NKT cell activation and influenza virus vaccination boosts memory CTL generation and protective immunity. Proc Natl Acad Sci U S A 106(9):3330–3335CrossRefPubMedCentralPubMedGoogle Scholar
- Kamijuku H, Nagata Y, Jiang X, Ichinohe T, Tashiro T, Mori K, Taniguchi M, Hase K, Ohno H, Shimaoka T, Yonehara S, Odagiri T, Tashiro M, Sata T, Hasegawa H, Seino KI (2008) Mechanism of NKT cell activation by intranasal coadministration of α-galactosylceramide, which can induce cross-protection against influenza viruses. Mucosal Immunol 1(3):208–218CrossRefPubMedGoogle Scholar
- Nieda M, Okai M, Tazbirkova A, Lin H, Yamaura A, Ide K, Abraham R, Juji T, Macfarlane DJ, Nicol AJ (2004) Therapeutic activation of Vα24+Vβ11+ NKT cells in human subjects results in highly coordinated secondary activation of acquired and innate immunity. Blood 103(2):383–389CrossRefPubMedGoogle Scholar
- Rigaud S, Fondaneche MC, Lambert N, Pasquier B, Mateo V, Soulas P, Galicier L, Le Deist F, Rieux-Laucat F, Revy P, Fischer A, de Saint Basile G, Latour S (2006) XIAP deficiency in humans causes an X-linked lymphoproliferative syndrome. Nature 444(7115):110–114. doi: 10.1038/nature05257
- Semmling V, Lukacs-Kornek V, Thaiss CA, Quast T, Hochheiser K, Panzer U, Rossjohn J, Perlmutter P, Cao J, Godfrey DI, Savage PB, Knolle PA, Kolanus W, Forster I, Kurts C (2010) Alternative cross-priming through CCL17-CCR4-mediated attraction of CTLs toward NKT cell-licensed DCs. Nat Immunol 11(4):313–320CrossRefPubMedGoogle Scholar
- Shimizu K, Mizuno T, Shinga J, Asakura M, Kakimi K, Ishii Y, Masuda K, Maeda T, Sugahara H, Sato Y, Matsushita H, Nishida K, Hanada K, Dorrie J, Schaft N, Bickham K, Koike H, Ando T, Nagai R, Fujii SI (2013) Vaccination with antigen-transfected, NKT cell ligand-loaded, human cells elicits robust in situ immune responses by dendritic cells. Cancer Res 73(1):62–73. doi: 10.1158/0008-5472.CAN-12-0759
- Van Kaer L (2007) NKT cells: T lymphocytes with innate effector functions. Curr Opin Immunol 19(3):354–364. doi: 10.1016/j.coi.2007.03.001
- Youn HJ, Ko SY, Lee KA, Ko HJ, Lee YS, Fujihashi K, Boyaka PN, Kim SH, Horimoto T, Kweon MN, Kang CY (2007) A single intranasal immunization with inactivated influenza virus and α-galactosylceramide induces long-term protective immunity without redirecting antigen to the central nervous system. Vaccine 25(28):5189–5198CrossRefPubMedGoogle Scholar