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Cancer Immunology, Immunotherapy

, Volume 30, Issue 1, pp 43–50 | Cite as

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

  • William E. Fogler
  • Lee K. Sun
  • Mark R. Klinger
  • John Ghrayeb
  • Peter E. Daddona
Original articles

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.

Keywords

Colon Carcinoma Colorectal Cancer Cell Peripheral Blood Monocyte Human Colorectal Cancer Biological Characterization 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • William E. Fogler
    • 1
  • Lee K. Sun
    • 2
  • Mark R. Klinger
    • 1
  • John Ghrayeb
    • 2
  • Peter E. Daddona
    • 1
  1. 1.Department of Immunobiology, Research and DevelopmentCentocor Inc.MalvernUSA
  2. 2.Department of Molecular Biology, Research and DevelopmentCentocor Inc.MalvernUSA

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