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Curative effects of combination therapy with lentinan and interleukin-2 against established murine tumors, and the role of CD8-positive T cells

  • Original Articles
  • IL-2, Lentinan, Synergistic Antitumor Effects, Tumor-Specific CTL
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Abstract

The antitumor activity of a combination of an antitumor polysaccharide, lentinan (a β1–3 glucan with β1–6 branches), and interleukin-2 (IL-2) was evaluated against established MBL-2 lymphoma and S908.D2 sarcoma at i.d. sites. Treatment of the MBL-2-tumor-bearing BDF1 mice with lentinan and IL-2 induced complete regression of tumor in 87.5% of mice treated. In contrast, treatments using either lentinan or IL-2 alone failed to induce complete regression of tumor, although temporal growth inhibition of tumor was observed about in half of the mice treated. Improvements of antitumor effects by the combination of lentinan and IL-2 were also observed in the MBL-2/B6 and S908.D2/B10.D2 systems. Expression of the antitumor effects of lentinan/IL-2 treatments required the intact T cell compartment, because the effects were not observed when nude mice were used. In the MBL-2/B6 system, the antitumor action of lentinan/IL-2 treatment was abolished in mice treated with antibody to CD8 antigen, whereas antibodies to CD4 or NK1.1 were ineffective. Furthermore, augmented tumor-specific cytotoxic T lymphocyte (CTL) activity was observed in regional lymph node cells of the mice after lentinan and IL-2 administration. These data indicate that the antitumor effects of lentinan/IL-2 are mediated by CD8+ CTL but not by CD4+ T cells or NK1.1+ NK/LAK cells, and suggest that this combined therapy may be effective against even established tumors that are resistant to IL-2 therapy.

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Abbreviations

B6:

C57BL/6

BDF1:

C57BL/6 × DBA/2 F1

Lyt2:

murine CD8α, Lyt2.1. allele of murine CD8

Lyt2.2:

allele of murine CD8

Lyt3:

murine CD8β

L3T4:

murine CD4

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Authors and Affiliations

  1. Basic Research Laboratories, Central Research Laboratories, Ajinomoto Co. Inc., 1-1, Suzuki-cho, Kawasaki-ku, 210, Kawasaki, Japan

    Manabu Suzuki, Tomoko Kikuchi, Fumihiko Takatsuki & Junji Hamuro

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  1. Manabu Suzuki
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  2. Tomoko Kikuchi
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  3. Fumihiko Takatsuki
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  4. Junji Hamuro
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Suzuki, M., Kikuchi, T., Takatsuki, F. et al. Curative effects of combination therapy with lentinan and interleukin-2 against established murine tumors, and the role of CD8-positive T cells. Cancer Immunol Immunother 38, 1–8 (1994). https://doi.org/10.1007/BF01517163

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  • DOI: https://doi.org/10.1007/BF01517163

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