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Antitumor response to recombinant murine interferon γ correlates with enhanced immune function of organ-associated, but not recirculating cytolytic T lymphocytes and macrophages

  • Original Articles
  • Murine Interferon γ, Antitumor Response, Organ-Associated CTL, Macrophages, Immunotherapy
  • Published:
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Abstract

The mechanism of therapeutic activity for recombinant murine interferon-γ(rMu IFNγ) in the treatment of metastatic disease was investigated by comparing effector cell augmentation with therapeutic activity in mice bearing experimental lung metastases (B16-BL6 melanoma). Effector cell functions in spleen, peripheral blood, and lung (the tumor-bearing organ) were tested after 1 week and 3 weeks of rMu IFNγ administration (i.v. three times per week). Natural killer (NK), lymphokine-activated killer (LAK), cytolytic T lymphocyte (CTL) activities against specific and nonspecific targets, and macrophage tumoristatic activity were measured. rMu IFNγ demonstrated immunomodulatory activity in most assays of immune function. The optimal therapeutic protocol of rMu IFNγ (2.5×106 U/kg, three times per week) prolonged survival and decreased the number of pulmonary metastatic foci. This therapeutic activity was correlated with specific CTL activity from pulmonary parenchymal mononuclear cells (PPMC), but not from spleen or blood. Macrophage tumoristatic activity in PPMC also correlated with therapeutic activity, but activity in alveolar macrophages did not. However, therapeutic activity did not correlate with NK or LAK activity at any site. These results demonstrate that the optimal therapeutic protocol is the same as the optimal immunomodulatory dose for pulmonary CTL and macrophage activities. Furthermore, while immunological monitoring may help to optimize treatment protocols, current monitoring procedures that use readily accessible sites, particularly peripheral blood, may not accurately predict the therapeutic efficacy of biological response modifiers in clinical trials.

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Author notes

  1. Hamblin Phillips, Henry R. Tribble & Robin Pennington

    Present address: NIH-FCRDC, Program Resources Inc., 21702-I201, Frederick, MD, USA

  2. Mark schneider

    Present address: Smith Kline and French Laboratories, 19406, King of Prussia, PA, USA

  3. James E. Talmadge

    Present address: Department of Pathology, University of Nebraska Medical Center, 6898-3135, Omaha, Nebraska, USA

Authors and Affiliations

  1. Division of Antiviral Drug Products, U.S. Food and Drug Administration, HFD-530, 5600 Fishers Lane, 20857, Rockville, Maryland, USA

    Paul L. Black, Hamblin Phillips, Henry R. Tribble, Robin Pennington, Mark schneider & James E. Talmadge

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  1. Paul L. Black
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  2. Hamblin Phillips
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  3. Henry R. Tribble
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  5. Mark schneider
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By acceptance of this article, the publisher or recipient acknowledges the right of the US. Government to retain a nonexclusive, royalty-free license in and to any copyright covering the article

This research was sponsored by the DHHS, under contract N01-23910 with Program Resources Inc. The contents of this publication do not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government

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Black, P.L., Phillips, H., Tribble, H.R. et al. Antitumor response to recombinant murine interferon γ correlates with enhanced immune function of organ-associated, but not recirculating cytolytic T lymphocytes and macrophages. Cancer Immunol Immunother 37, 299–306 (1993). https://doi.org/10.1007/BF01518452

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  • DOI: https://doi.org/10.1007/BF01518452

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