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Protective specific immunity induced by cyclophosphamide plus tumor necrosis factor α combination treatment of EL4-lymphoma-bearing C57BL/6 mice

  • Original Article
  • Drug therapy, Immunotherapy, Cyclophosphamide, TNFα
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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

An Erratum to this article was published on 01 October 1997

Abstract

A combination treatment protocol initiated 12 days after tumor injection, when the tumor was large, by administering cyclophosphamide (CY, 150 or 250 mg/kg) intraperitoneally followed by intravenous tumor necrosis factor α (TNFα, 1000 units/injection) on days 13, 16, 18, 21, and 23, resulted in about 60% longterm survival (i.e., survival for at least 60 days) in the syngeneic C57BL/6 mouse/EL4 lymphoma model system. The establishment of a specific antitumor immune memory and its possible therapeutic relevance was verified by reinjecting 60-day survivors with EL4 cells; all 60-day survivors that had received the combination treatments rejected the implants and survived for a further 60 days. Thymic cellularity was reduced during treatment and its recovery appeared to correlate with long-term survival and immunity. Thymocytes from mice treated with the combination were found to express significant levels of specific anti-EL4 cytolytic activity following a 4-day stimulation culture with X-irradiated EL4 cells and low concentrations of interleukin-2. This response could not be generated with thymocytes from naive animals. In each case the effect seen with the combination of a moderate CY dose (150 mg/kg) with TNFα was better than that seen with either dose of CY alone and equal to or better than that seen with the higher dose of CY combined with TNFα. These results indicate that treatment with a single moderate dose of CY in combination with TNFα is effective against a large, established tumor in this murine model. Furthermore, all the long-term survivors induced by this treatment developed protective immunity against reimplanted tumor and demonstrated a long-term specific immune memory in the thymus.

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Authors and Affiliations

  1. Department of Experimental Therapeutics, Grace Cancer Drug Center, Roswell Park Cancer Institute, Elm and Carlton Streets, 14263, Buffalo, NY, USA

    Christian M. Krawczyk, Srdan Verstovšek, Peter Ujházy, Darbie Maccubbin & M. Jane Ehrke

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  1. Christian M. Krawczyk
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  2. Srdan Verstovšek
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  3. Peter Ujházy
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  4. Darbie Maccubbin
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  5. M. Jane Ehrke
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Additional information

This work was done in partial fulfillment of the M.S. degree requirements (C. M. K.) in the Program of Natural Sciences, Roswell Park Graduate Division, SUNY at Buffalo

An erratum to this article is available at http://dx.doi.org/10.1007/s002620050401.

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Krawczyk, C.M., Verstovšek, S., Ujházy, P. et al. Protective specific immunity induced by cyclophosphamide plus tumor necrosis factor α combination treatment of EL4-lymphoma-bearing C57BL/6 mice. Cancer Immunol Immunother 40, 347–357 (1995). https://doi.org/10.1007/BF01525385

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  • DOI: https://doi.org/10.1007/BF01525385

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