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Biological characterization of a chimeric mouse-human IgM antibody directed against the 17-1A antigen

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Summary

A chimeric antibody was constructed in which the murine H- and L-chain variable regions of mAb 17-1A, raised against human colorectal cancer cells, were joined with the human constant μ and κ regions. Transfection of these constructs into the murine myeloma Sp2/0 resulted in the expression and secretion of a pentameric Ig, designated chimeric 17-1A IgM. The chimeric 17-1A IgM was subsequently compared to a previously described chimeric 17-1A IgG1 for biological activities. Both chimeric mAbs were equally effective (weight basis) in competing against the binding of murine125I-17-1A to cultures of HT-29 colon carcinoma cells. The calculated association constants for the chimeric 17-1A IgM and IgG1 were 1.63 × 108 1/mol and 3.41 × 107 1/mol, respectively. Unlike chimeric 17-1A IgG1, the chimeric 17-1A IgM was able to render colon carcinoma target cells susceptible to lysis by both xenogeneic (rabbit) and human complement. The extent of complement-mediated lysis dependent upon chimeric 17-1A IgM was correlated to 17-1A antigen expression on target cells. HT-29 colon carcinoma cells treated with chimeric 17-1A IgM did not directly result in antibody-dependent cellular cytotoxicity by human peripheral blood monocytes. However, chimeric 17-1A IgM greatly enhanced the deposition of C3 on complementtreated HT-29 cells, and concomitant incubation with monocytes resulted in heightened lysis of the tumor cells. The feasibility of enhancing host defense against gastrointestinal malignancies by the administration of this chimeric 17-1A IgM may have certain clinical advantages.

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Authors and Affiliations

  1. Department of Immunobiology, Research and Development, Centocor Inc., 244 Great Valley Parkway, 19355, Malvern, PA, USA

    William E. Fogler, Mark R. Klinger & Peter E. Daddona

  2. Department of Molecular Biology, Research and Development, Centocor Inc., 244 Great Valley Parkway, 19355, Malvern, PA, USA

    Lee K. Sun & John Ghrayeb

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  1. William E. Fogler
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  2. Lee K. Sun
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  3. Mark R. Klinger
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  4. John Ghrayeb
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  5. Peter E. Daddona
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Fogler, W.E., Sun, L.K., Klinger, M.R. et al. Biological characterization of a chimeric mouse-human IgM antibody directed against the 17-1A antigen. Cancer Immunol Immunother 30, 43–50 (1989). https://doi.org/10.1007/BF01665029

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  • DOI: https://doi.org/10.1007/BF01665029

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