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Immunization with mutagen-treated (tum−) cells causes rejection of nonimmunogenic rat glioma isografts

  • Original Articles
  • IFNγ, Immunization, Immunogenicity, Isograft Rejection, Mutagen Treatment, Rat Brain Tumor
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Abstract

The ethyl-N-nitrosourea-induced rat glioma N32 was treated with the mutagenic compoundN-methyl-N′-nitro-N-nitrosoguanidine and the surviving cells cloned by limiting dilution. Out of 20 clones tested 8 did not produce tumors subcutaneously even after challenge doses 3 log units above the minimal tumor dose for N32. All of 5 clones grew in a retarded manner intracerebrally but produced tumors in some animals. Preimmunizations with three of the rejected clones (tum−) gave protection against subcutaneous and intracerebral isografts of the unmutated N32. This effect could be enhanced if the cells used for immunizations were pretreated with interferon γ (IFNγ) for 48 h. If immunizations were started subsequent to challenge, only immunization with one of two tested tum− clones pretreated with IFNγ induced significant rejection against intracerebral N32 isografts. Both N32 and its tum− closes were MHC class I positive and MHC class II negative. IFNγ treatment enhanced the MHC class I expression with 20%–90% on the tum− clones and with 40% on N32. MHC class II expression could be induced on N32 cells after 7 days of IFNγ treatment but not on any of the tum− clones tested. We conclude that the enhancing effect of IFNγ treatment on tumor isograft rejection may depend on up-regulation of MHC class I but not of MHC class II. This investigation demonstrates that it is possible to induce rejection of weakly immunogenic intracerebral brain tumors by immunization with selected highly immunogenic tumor cell mutants. In conjunction with relevant cytokines, the cross-protective effect of these tum− variants might be further enhanced and serve as a model for immunotherapy against malignant human brain tumors.

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Authors and Affiliations

  1. Department of Tumorimmunology, The Wallenberg Laboratory, University of Lund, Box 7031, S-220 07, Sweden

    Peter Siesjö, Edward Visse, Magnus Lindvall & Hans Olov Sjögren

  2. Department of Neurosurgery, University of Lund, Sweden

    Peter Siesjö & Leif Salford

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  1. Peter Siesjö
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Siesjö, P., Visse, E., Lindvall, M. et al. Immunization with mutagen-treated (tum−) cells causes rejection of nonimmunogenic rat glioma isografts. Cancer Immunol Immunother 37, 67–74 (1993). https://doi.org/10.1007/BF01516944

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  • DOI: https://doi.org/10.1007/BF01516944

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