Abstract
The clinical and immunologic effects of murine monoclonal antibody (mAb) CC49 administered at a low dose sequentially with granulocyte-macrophage colony-stimulating factor (GM-CSF) were examined. Fourteen patients with metastatic colorectal cancer received 1 mg of unconjugated CC49 on day 1; on day 15 they began 125 micrograms/m2 GM-CSF by subcutaneous injection daily for 14 days, followed by 7 days of rest. Another 14 days of GM-CSF were then administered, followed by 7 days of rest. This 56-day cycle was repeated in patients whose cancer did not progress. Therapy was well tolerated; adverse allergic reactions were not observed. Objective tumor responses were not observed. Increases in antiidiotypic (T2) and anti-antiidiotypic (T3) cellular responses were observed, as were increases in human antimouse antibody levels. In contrast, the expression of Fc receptors on CD14+ peripheral blood monocytes decreased. This pilot study demonstrates idiotypic cellular immunologic effects of antitumor murine mAb, even at the doses used for imaging, and supports the sequential administration of GM-CSF as an adjuvant to mAb-based immunogens.
Publication types
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Clinical Trial
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Aged
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Animals
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Antibodies, Anti-Idiotypic / immunology
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Antibodies, Monoclonal / administration & dosage*
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Antibodies, Monoclonal / adverse effects
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Antibodies, Monoclonal / pharmacology
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Antibodies, Monoclonal / therapeutic use
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Antibodies, Neoplasm / administration & dosage*
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Antibodies, Neoplasm / adverse effects
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Antibodies, Neoplasm / pharmacology
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Antibodies, Neoplasm / therapeutic use
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Colorectal Neoplasms / immunology
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Colorectal Neoplasms / pathology
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Colorectal Neoplasms / therapy*
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Drug Administration Schedule
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Female
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Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage*
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Granulocyte-Macrophage Colony-Stimulating Factor / adverse effects
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Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
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Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use
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Humans
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Immunity, Cellular / drug effects
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Immunotherapy*
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Leukocyte Count / drug effects
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Male
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Mice
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Middle Aged
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Neoplasm Metastasis
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Pilot Projects
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Recombinant Proteins
Substances
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Antibodies, Anti-Idiotypic
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Antibodies, Monoclonal
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Antibodies, Neoplasm
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B72.3 antibody
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Recombinant Proteins
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Granulocyte-Macrophage Colony-Stimulating Factor