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Influence of antibody protein dose on therapeutic efficacy of radioiodinated antibodies in nude mice bearing GW-39 human tumor

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Summary

The biodistributions of three131I-labeled murine monoclonal antibodies, NP-4 and Immu-14 anti-(carcinoembryonic antigen), and Mu-9 anti-(colon-specific antigen p), were determined at antibody protein doses varying from 1 µg to 1000 µg in nude mice with small (0.1–0.4 g) GW-39 human colonic cancer xenografts. For each antibody, the percentage of the injected dose per gram of tumor and tumor/nontumor ratios were constant over a wide protein dose range. However, at high protein doses (above 100 µg for NP-4 and Immu-14) the percentage of the injected dose per gram of tumor and tumor/nontumor ratios decreased. Assuming that the uptake of a control anti-(α-fetoprotein) antibody represents the amount of antibody that accumulates in the tumor nonspecifically (i.e., antigen-independently), it could be shown that for each antibody the amount of antibody protein that accumulates in the tumor specifically, increases linearly with the protein dose, reaching a plateau level at the highest doses tested. The growth inhibition of GW-39 tumor transplants in nude mice treated with131I-labeled antibody at either low or high antibody protein dose was compared. These experiments indicated that, in this experimental model, enhanced antibody protein dose may decrease the therapeutic efficacy of radioiodinated antibodies. It is suggested that heterogeneous distribution at low protein dose, with intense localization around the blood vessels, may enhance the tumoricidal effect of radioantibodies.

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Authors and Affiliations

  1. Garden State Cancer Center and Center for Molecular Medicine and Immunology, 1 Bruce Street, 07 103, Newark, NJ, USA

    Otto C. Boerman, Robert M. Sharkey, George Y. Wong, Rosalyn D. Blumenthal, Rosarito L. Aninipot & David M. Goldenberg

  2. Memorial Sloan-Kettering Cancer Center, New York, N. Y., USA

    George Y. Wong

Authors
  1. Otto C. Boerman
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  2. Robert M. Sharkey
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  3. George Y. Wong
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  4. Rosalyn D. Blumenthal
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  5. Rosarito L. Aninipot
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  6. David M. Goldenberg
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Additional information

Supported in part by USPHS grants CA 39 841 and CA 37 895, National Institutes of Health and Human Services

Research fellow of the Dutch Cancer Society

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Boerman, O.C., Sharkey, R.M., Wong, G.Y. et al. Influence of antibody protein dose on therapeutic efficacy of radioiodinated antibodies in nude mice bearing GW-39 human tumor. Cancer Immunol Immunother 35, 127–134 (1992). https://doi.org/10.1007/BF01741860

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  • DOI: https://doi.org/10.1007/BF01741860

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