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Augmentation of the therapeutic efficacy of adoptive tumor immunotherapy by in vivo administration of slowly released recombinant interleukin 2

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Summary

Immunization of C57BL/6 mice with MMC-treated syngeneic lymphoma cells, MBL-2, caused the generation of antitumor effector cells in vivo and the immunized mice permanently rejected viable MBL-2 lymphoma cells. Both plastic nonadherent T cells and plastic adherent MØ obtained from MBL-2 immunized mouse peritoneal exudate cells revealed strong cytotoxic activity against MBL-2 lymphoma cells, whereas immune spleen cells were not highly active against MBL-2 lymphoma cells in vitro. However, systemic adoptive transfer of immune spleen cells into the MBL-2-bearing mice by i.v. infusion in conjunction with i.p. cyclophosphamide (100 mg/kg) treatment cured the mice of tumor. This therapeutic efficacy of immune spleen cells was reflected by the number of transferred effector cells and over 5×107 immune spleen cells were required to cure the mice completely. The cells mediating in vivo rejection of MBL-2 lymphoma cells were Thy 1.2+ T cells. This ACIT was specific against MBL-2 lymphoma cells and had no effect on the growth of other syngeneic tumors, B16 melanoma or BMC6A fibrosarcoma. In vivo administration of recombinant interleukin 2 (r-IL 2) combined with ACIT greatly modulated the cure rate of tumor-bearing mice. In addition, we found that slowly released r-IL 2 administratered from an ALZET miniosmotic pump was more effective in augmenting the therapeutic efficacy of immune spleen cells in ACIT than a single injection of the same total dose of r-IL 2.

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Authors and Affiliations

  1. Department of Hygienic Chemistry, Pharmaceutical Institute, Tohoku University, Aobayama, 980, Sendai, Japan

    Takashi Nishimura, Yuji Togashi, Makiko Goto, Hideki Yagi, Yasushi Uchiyama & Yoshiyuki Hashimoto

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  1. Takashi Nishimura
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  2. Yuji Togashi
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  3. Makiko Goto
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  4. Hideki Yagi
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  5. Yasushi Uchiyama
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  6. Yoshiyuki Hashimoto
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Nishimura, T., Togashi, Y., Goto, M. et al. Augmentation of the therapeutic efficacy of adoptive tumor immunotherapy by in vivo administration of slowly released recombinant interleukin 2. Cancer Immunol Immunother 21, 12–18 (1986). https://doi.org/10.1007/BF00199371

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  • DOI: https://doi.org/10.1007/BF00199371

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