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Granulocyte/macrophage-colony-stimulating factor augments the induction of antibodies, especially anti-idiotypic antibodies, to therapeutic monoclonal antibodies

  • Original Article
  • Monoclonal Antibodies HAMA, Antidiotypic Antibodies, GM-CSF Colorectal Carcinoma
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Abstract

A group of 86 patients with advanced colorectal carcinoma were treated with the mouse (m) (IgG2A) or chimeric (c) monoclonal antibody (mAb) 17-1A. Prior to therapy, no patient had detectable levels of antibodies to mAb17-1A. All mmAb17-1A-treated patients (n=76) developed antibodies against both idiotypic and isotypic determinants. Addition of granulocyte/macrophage-colony-stimulating factor (GM-CSF) to mmAb17-1A significantly enhanced the induction of anti-idiotypic (ab2) as well as anti-isotypic antibodies. Of the mmAb17-1A-treated patients, 16 developed type I allergic reactions. These patients had significantly higher concentrations of anti-(mouse Ig) antibodies than patients without type I reactions. Of these 16 patients, 5 had received mmAb17-1A alone; they constituted 9% of this group (5/56). The remaining 11 patients had been given mmAb17-1A together with GM-CSF, and represented 55% of this treatment group (11/20). The difference was statistically significant (P<0.001). Of 10 patients, 9 (90%) treated with cmAb17-1A and GM-CSF developed ab2. The ab2 concentration in this patient group was significantly lower compared to those treated with mmAb-17A. Anti-(mouse Ig) antibodies caused clinical symptoms requiring therapeutic intervention in fewer than 10% of the patients treated with mmAb17-1A alone. With the addition of GM-CSF, the antibody concentration as well as the frequency of allergic side-effects calling for medical action increased significantly. Significantly more patients with a high ab2 concentration (at least 15μg/ml) 1 month after completion of mAb therapy responded to mAb treatment as compared to those with a low ab2 concentration (P<0.05). Moreover, patients with a high ab2 concentration (at least 15 μg/ml) had a median survival time of 15 months while those with a lower concentration survived for a median time of 9 months (P=0.01).

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Authors and Affiliations

  1. Department of Oncology (Radiumhemmet) and Immunological Research Laboratory, Karolinska Hospital, S-171 76, Stockholm, Sweden

    Peter Ragnhammar, Jan Fagerberg, Jan-Erik Frödin, Peter Wersäll & Hakan Mellstedt

  2. Department of Clinical Chemistry, Karolinska Hospital, Stockholm, Sweden

    Lars-Olof Hansson

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  1. Peter Ragnhammar
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  2. Jan Fagerberg
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  3. Jan-Erik Frödin
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  4. Peter Wersäll
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  5. Lars-Olof Hansson
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  6. Hakan Mellstedt
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Ragnhammar, P., Fagerberg, J., Frödin, JE. et al. Granulocyte/macrophage-colony-stimulating factor augments the induction of antibodies, especially anti-idiotypic antibodies, to therapeutic monoclonal antibodies. Cancer Immunol Immunother 40, 367–375 (1995). https://doi.org/10.1007/BF01525387

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  • DOI: https://doi.org/10.1007/BF01525387

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