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Specific eradication of micrometastases by transfer of tumour-immune T cells from major-histocompatibility-complex congenic mice

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Summary

DBA/2 (H-2d) mice bearing a transplanted highly metastatic lymphoma (ESb) in a state of widely disseminated disease could be successfully treated by a combination of surgery (removal of the local tumour), irradiation (5 Gy) and adoptive immunotherapy. The immunotherapy was achieved by transfer of anti-ESb-immune spleen cells from B10.D2 mice, which express the same major histocompatibility complex (MHC) molecules as DBA/2. In contrast, anti-ESb-immune cells from MHC-disparate C57BL/6 mice did not confer protective immunity. The B10.D2 anti-ESb-immune T cells contain two types of cytolytic specificity as detected by limiting-dilution analysis: (1) clones with specificity for the ESb-tumour-associated transplantation antigen (TATA) (at low frequency), and (b) clones with specificity for minor DBA/2 histocompatibility (H) antigens (at high frequency). Immune B10.D2 cells raised against different tumour lines or against TATA− ESb tumour variants did not confer the 100% protection seen with immune cells against ESb TATA+ cells. Finally we demonstrate that the allogeneic immune cells are more potent in terms of protective immunity than corresponding syngeneic immune cells. The data suggest that the strong graft-versus-leukemia effect with immune T cells from allogeneic MHC-identical but not from MHC-disparate mice was due to T cells with MHC-restricted specificity for an ESb-associated TATA. A graft-versus-host reactivity that developed much later and could not be prevented was most likely due to T cells sensitized against normal minor H antigens of the host. Our results are of potential relevance for allogeneic bone marrow transplantation and adoptive immunotherapy protocols.

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  1. Paul von Hoegen & Hans-Jörg Schild

    Present address: Medical Center, Stanford University, 94 305, Stanford, California, USA

Authors and Affiliations

  1. Institut für Immunologie und Genetik, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, W-6900, Heidelberg, Germany

    Volker Schirrmacher, Paul von Hoegen, Andreas Griesbach, Hans-Jörg Schild & Uwe Zangemeister-Wittke

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  1. Volker Schirrmacher
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  2. Paul von Hoegen
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  4. Hans-Jörg Schild
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  5. Uwe Zangemeister-Wittke
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Schirrmacher, V., von Hoegen, P., Griesbach, A. et al. Specific eradication of micrometastases by transfer of tumour-immune T cells from major-histocompatibility-complex congenic mice. Cancer Immunol Immunother 32, 373–381 (1991). https://doi.org/10.1007/BF01741332

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  • DOI: https://doi.org/10.1007/BF01741332

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