Laboratory for Immunotherapy

A various types of immune cells attack the cancer or infected cells in cancer or infection with pathogenic organism in the host. However, it is often uncontrollable.

We have developed an artificial adjuvant vector cells (aAVC) as new type of drug delivery system. When transferred in vivo, it leads to the adaptive immunity through the NKT cell-induced DC maturation in situ.

The final goal of our team is to extend the basic study for advancing immunotherapy and the translational research, from basic studies back and forth to the bed side in the field of cancer and the control of other diseases.

Research Fields

Materials Sciences / Immunology / Clinical Medicine

Research Subjects

• Development of artificial adjuvant vector cells
• Analysis of dendritic cells in situ linking innate and adaptive immunity
• Immune tolerance in the cancer and infectious diseases

Publications

1. Shimizu, K., Asakura, M., Shinga, J., Sato, Y., Kitahara, S., Hoshino, K., Kaisho, T., Schoenberger, SP., Ezaki, T., and Fujii, S.:
   Invariant NKT cells induce plasmacytoid DC cross-talk with conventional DCs for efficient memory CD8+ T cell induction.
   (in press)
2. Fujii S and Shimizu K.:
   "Immunotherapy with artificial adjuvant vector cells (aAVCs): harnessing both arms of the immune response."
   OncoImmunol 2013 (in press)
3. Vizcardo R, Masuda K, Yamada D, Ikawa T, Shimizu K, Fujii S, Koseki H, Kawamoto H.:
   "Regeneration of antigen-specific T cells from iPS cells derived from human CD8⁺ mature T cells."
   Cell Stem Cell 2012, 12:31-36.
4. 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 KI, Dörrie J, Schaft N, Bickham K, Koike H, Ando T, Nagai R, Fujii S.:
   "Vaccination with antigen-transfected, NKT cell ligand-loaded, human cells elicits robust in situ immune responses by dendritic cells."
   Cancer Res. 2013, 73:62-73.
5. Shimizu K, Asakura M, Fujii S.:
   "Prolonged antitumor NK cell reactivity elicited by CXCL-10-expressing dendritic cells licensed by CD40L⁺CD4⁺ memory T cells."
   J. Immunol. 2011:186:5927-37.
6. Asano K, Nabeyama A, Miyake Y, Qiu CH, Kurita A, Tomura M, Kanagawa O, Fujii S, Tanaka M.:
   "CD169-Positive Macrophages Dominate Antitumor Immunity by Crosspresenting Dead Cell-Associated Antigens."
   Immunity 2011, 34:85-95.
7. Watarai H, Fujii S, Yamada D, Rybouchkin A, Sakata S, Nagata Y, Iida-Kobayashi M, Sekine-Kondo E, Shimizu K, Shozaki Y, Sharif J, Matsuda M, Mochiduki S, Hasegawa T, Kitahara G, Endo TA, Toyoda T, Ohara O, Harigaya K, Koseki H, Taniguchi M.:
   "Murine induced pluripotent stem cells can be derived from and differentiate into natural killer T cells."
   J Clin Invest.:2010, 120:2610-8.
8. Watarai H, Rybouchkin A, Hongo N, Nagata Y, Sakata S, Sekine E, Dashtsoodol N, Tashiro T, Fujii S, Shimizu K, Mori K, Masuda K, Kawamoto H, Koseki H, Taniguchi M.:
   "Generation of functional NKT cells in vitro from embryonic stem cells bearing rearranged invariant Valpha14-Jalpha18 TCRalpha gene."
   Blood 2010, 115:230-7.
9. Fujii S, Goto A, Shimizu K.:
   "Antigen mRNA-transfected, allogeneic fibroblasts loaded with NKT-cell ligand confer antitumor immunity."
   Blood 2009, 113:4262-72.
10. Shimizu K and Fujii S.:
    "Dendritic cell therapy induces long term NK reactivity to tumors via host dendritic cells."
    Eur J Immunol. 2009, 39: 457-68.