Clinical Immunotherapeutics

, Volume 5, Issue 4, pp 294–308 | Cite as

Monocyte/Macrophage Activation by Immunostimulators

Role in Cancer Therapy
  • Burkhard Hennemann
  • Reinhard Andreesen
Review Article Immunological Basis of Disease

Summary

Cells of the monocyte/macrophage lineage are considered to be of special importance in host defence against tumour growth. There is experimental and clinical evidence that in malignant disease the generation of cytotoxic macrophages is impaired. Both defective cell maturation and loss of responsiveness to activation have been described. Immunotherapeutic strategies to stimulate macrophage tumour cytotoxicity make use of activating compounds such as interferon-γ (IFNγ), endotoxin (lipopolysaccharide) and other cytokines that are administered systemically.

Subcutaneous treatment with low-dose IFNγ given on a weekly schedule achieved an objective response of 4 to 30% in patients with metastatic renal cell carcinoma. Higher doses of IFNγ were given intravenously and achieved an objective response in 9% and stable disease in 49% of patients with renal cell carcinoma. Lipopolysaccharide given intravenously induced a profound immunological response in the recipient. Antitumour activity was seen in 25% of patients with advanced cancer.

Adoptive immunotherapy with macrophages generated in vitro is a treatment modality designed to correct for defective in vivo maturation of monocytes. Preclinical data in murine models showed a remarkable antitumour effect of transferred cells. Activated macrophages given locally or via intravenous injection inhibited tumour growth of Lewis lung carcinoma by 30 to 40% in C57B16 mice. Clinical trials with local and systemic transfer of autologous cytotoxic macrophages showed the induction of neopterin, interleukin-6 and thrombin-antithrombin complexes in the recipient. The antitumour activity of local therapy was evident from the disappearance of malignant ascites upon intraperitoneal cell application. However, as reported by several groups, intravenous cell transfer has yielded conflicting results and only minor tumour responses were seen. Here, further improvements in culture technique and mode of cell activation are being developed.

In addition, macrophages could be used as a target of gene transfer experiments. The therapeutic value of this technique needs careful investigation.

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Copyright information

© Adis International Limited 1996

Authors and Affiliations

  • Burkhard Hennemann
    • 1
  • Reinhard Andreesen
    • 1
  1. 1.Department of Hematology/Oncology, Klinik und Poliklinik für Innere Medizin IKlinikum der Universität RegensburgRegensburgGermany

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