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Biodistributions of intact monoclonal antibodies and fragments of BLCA-38, a new prostate cancer directed antibody

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Abstract

Background: Monoclonal antibodies (MAbs) are used for targeting agents to tumours while minimizing normal tissue exposure. Methods: A new anti–prostate cancer MAb, BLCA-38, was radioiodinated (I125) and assessed for its ability to target subcutaneous human prostate cancer (DU-145) xenografts after systemic intraperitoneal administration. For comparison, the profile of J591 MAb (now in clinical trial) against LNCaP-LN3 tumours was examined. Biodistribution profiles were obtained at various times, by assessing injected dose/gram (%ID/g) and xenograft to blood (X/B) ratios. Microautoradiography of xenografts was performed. After conjugation with a melittin peptide toxin, the profiles of BLCA-38 and J591 were compared with that of an irrelevant antibody, DS-1. Results: Xenograft localization by 125I-labeled BLCA-38 and J591 MAbs to their relevant antigen-positive tumors was comparable, and there was no unusual localization in nontumour tissues. F(ab’)2 and Fab fragments gave improved X/B ratios, but the %ID/g xenograft was decreased and they accumulated in kidneys, bladder and stomach. In contrast, the conjugates of irrelevant antibody showed no tumour targeting. Microautoradiography showed more tumour accumulation of MAbs than F(ab’)2s or Fabs. Conclusions: BLCA-38 can target prostate cancer in vivo almost as effectively as J591. Given that J591 is used clinically, BLCA-38, which targets a different antigen, has potential for radioimmunoscintigraphy and for therapeutic targeting of prostate cancer.

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Acknowledgements

The authors thank Dr Neil Bander, Cornell University, New York, USA, and Millennium Pharmaceuticals for the J591 hybridoma. The work was financially supported by an AusIndustry grant and by Commonwealth Serum Laboratories (CSL). We gratefully acknowledge helpful discussions with Drs Peter Molloy and Jerome Werkmeister, CSIRO, Molecular Science, and Dr Simon Green, CSL.

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Authors and Affiliations

  1. School of Clinical Medicine, University of New South Wales, Sydney, Australia

    Teresa Carter, Katy Sterling-Levis, Kim Ow & Pamela J. Russell

  2. Oncology Research Centre, Prince of Wales Hospital, Barker St., Clinical Sciences Building, Level 2, NSW 2031, Randwick, Australia

    Teresa Carter, Katy Sterling-Levis, Kim Ow & Pamela J. Russell

  3. CSIRO Health Science and Nutrition, 3052, Parkville, Victoria, Australia

    Larissa Doughty, Meghan Hattarki, Deborah Shapira, Dean Hewish & Alexander A. Kortt

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  1. Teresa Carter
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  2. Katy Sterling-Levis
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Correspondence to Pamela J. Russell.

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Carter, T., Sterling-Levis, K., Ow, K. et al. Biodistributions of intact monoclonal antibodies and fragments of BLCA-38, a new prostate cancer directed antibody. Cancer Immunol Immunother 53, 533–542 (2004). https://doi.org/10.1007/s00262-003-0460-1

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