International Journal of Hematology

, Volume 73, Issue 3, pp 378–382 | Cite as

Antitumor Immunity Induced by Irradiated Tumor Cells Producing Macrophage Colony-Stimulating Factor

  • Shinya Suzu
  • Fumihiko Kimura
  • Miyuki Tanaka-Douzono
  • Muneo Yamada
  • Yukitsugu Nakamura
  • Naoki Wakimoto
  • Ken Sato
  • Toshiro Morita
  • Kazuma Ikeda
  • Kazuo Motoyoshi
Case Report


We previously reported that administration into mice of mouse lymphoid leukemia L1210 cells engineered to secrete macrophage colony-stimulating factor (M-CSF) could lead to tumor rejection. Here, we demonstrate that inoculation with irradiated M-CSF-producing cells protects mice against a subsequent challenge with unmodified parental tumor cells. We used 2 experimental protocols: the inoculation with irradiated M-CSF-producing L1210 cells (EM5) before the challenge with parental cells and after the challenge with parental cells. Both protocols effectively improved the survival rate of mice compared with protocols in which irradiated non-M-CSF-producing L1210 cells (EM-mock) were inoculated. Inoculation with 1 X 102 irradiated EM5 cells was sufficient to prolong the survival time of mice subsequently challenged with 1 X 104 parental cells. In vivo depletion experiments with administration of antibodies suggested the involvement of CD4+ T cells, CD8+ T cells, and natural killer (NK) cells in the antitumor effect. Consistent with these findings, the cytotoxic T lymphocyte activity of splenocytes from EM5-inoculated mice was higher than that from EM-mock-inoculated mice, and L1210 tumors were heavily infiltrated by CD4+ T cells and NK cells as well as macrophages in EM5-inoculated mice.

Key words

Macrophage colony-stimulating factor Immunotherapy Gene therapy Leukemia Tumor vaccine 


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Copyright information

© The Japanese Society of Hematology 2001

Authors and Affiliations

  • Shinya Suzu
    • 1
  • Fumihiko Kimura
    • 2
  • Miyuki Tanaka-Douzono
    • 1
  • Muneo Yamada
    • 1
  • Yukitsugu Nakamura
    • 2
  • Naoki Wakimoto
    • 2
  • Ken Sato
    • 2
  • Toshiro Morita
    • 3
  • Kazuma Ikeda
    • 4
  • Kazuo Motoyoshi
    • 2
  1. 1.Biochemical Research LaboratoryMorinaga Milk IndustryKanagawaJapan
  2. 2.Third Department of Internal MedicineNational Defense Medical CollegeSaitamaJapan
  3. 3.Health Science CenterKagawa UniversityKagawaJapan
  4. 4.Division of Blood TransfusionOkayama UniversityOkayamaJapan

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