Summary
Conjugates of the chemotactic peptide fMet-Leu-Phe (fMLP) to IgG retain chemotactic and antigen recognition function in vitro and enhance intra-tumour macrophage numbers in a guinea pig model. We report a study approved by the ethics committee on the acute toxicity of fMLP conjugates in ten consenting cancer patients with metastasizing melanoma and colon cancer. They were given increasing single doses (1–2500 µg) IgG-fMLP made with the anti-melanoma monoclonal antibody (mAb) 9.2.27. Clinical examinations and blood cell counts, urinalysis, electrolytes, and liver and kidney function tests before and after the infusion and weekly thereafter revealed no relevant toxicities. One patient had a herpes zooster exacerbation on day 1, which was judged to be coincidental. Peak post-infusion conjugate serum concentrations fell to unmeasurable levels within a few days. In no case was a human humoral anti-(mouse Ig) immune response detected.
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This work was supported by grant FOR.254.AK.83 of the Swiss Cancer League.
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Obrist, R., Schmidli, J., Müller, R. et al. Acute and subacute toxicity of chemotactic conjugates between monoclonal antibody and fMet-Leu-Phe in humans: A phase I clinical trial. Cancer Immunol Immunother 32, 406–408 (1991). https://doi.org/10.1007/BF01741336
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DOI: https://doi.org/10.1007/BF01741336