Skip to main content

Chimerization of a Monoclonal Antibody for Treating Hodgkin's Lymphoma

  • Protocol
Recombinant Antibodies for Cancer Therapy

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 207))

  • 910 Accesses

Abstract

Conventionally, monoclonal antibodies (MAbs) are generated by fusing B cells from an immunized animal with myeloma cells from the same species (1). Several murine MAb have already been employed for in vivo diagnosis and therapy, including Ber-H2 which recognizes the human CD30 molecule with high specificity and affinity (2). CD30, a member of the nerve growth factor (NGF) tumor necrosis factor receptor (TNFR) superfamily (3), is strongly expressed on the pathognomonic Hodgkin (H) and Reed-Sternberg (R-S) cells of Hodgkin’s lymphoma (4) and various non-Hodgkin lymphomas of either T- or B-cell type origin (5). Its reaction pattern in normal lymphoid tissue is restricted to a population of blastoid cells located around B-cell follicles and at the rim of germinal centers (2). Consequently, Ber-H2 has been utilized as an immunotoxin by conjugating the antibody to the ribosome-inactivating toxin Saporin to treat four patients with refractory Hodgkin’s lymphoma (6). However, despite remarkable tumor reductions of up to more than 75% were achieved after administration of one single dose of the reagent, patients developed an immune response against both the rodent immunoglobulin and the toxin moiety, precluding further application of the immunotoxin (6). In order to fully preserve the specificity of Ber-H2 and to overcome the aforementioned disadvantages, we have generated a chimeric mouse/human antibody.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Köhler G. and Milstein C. (1975). Continuous culture of fused cells secreting antibody of predefined specifity. Nature 256, 495–497.

    Article  PubMed  Google Scholar 

  2. Schwarting R., Gerdes J., Durkop H., Falini B., Pileri S., and Stein H. (1989). BER-H2: a new anti-Ki-1 (CD30) monoclonal antibody directed at a formol-resistant epitope. Blood 74, 1678–1689.

    PubMed  CAS  Google Scholar 

  3. Dürkop H., Latza U., Hummel M., Eitelbach F., Seed B., and Stein H. (1992). Molecular cloning and expression of a new member of the nerve growth factor receptor family that is charakteristic for Hodgkin’s disease. Cell 68, 421–427.

    Article  PubMed  Google Scholar 

  4. Schwab U., Stein H., Gerdes J., Lemke H., Kirchner H., Schaadt M., and Diehl V. (1982). Production of a monoclonal antibody specific for Hodgkin and Sternberg-Reed cells of Hodgkin’s disease and a subset of normal lymphoid cells. Nature 299, 65–67.

    Article  PubMed  CAS  Google Scholar 

  5. Stein H., Mason D. Y., Gerdes J., O’Connor N., Wainscoat J., Pallesen G., et al. (1985). The expression of the Hodgkin’s disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells. Blood 66, 848–858.

    PubMed  CAS  Google Scholar 

  6. Falini B., Bolognesi A., Flenghi L., Tazzari P. L., Broe M. K., Stein H., et al. (1992). 7/14/06 12:15PM. Lancet 339, 1195–1196.

    Article  PubMed  CAS  Google Scholar 

  7. Liu A. Y., Robinson R. R., Hellstrom K. E., Murray E. D., Chang C. P., and Hellstrom I. (1987). Chimeric mouse-human IgG1 antibody that can mediate lysis of cancer cells. Proc. Natl. Acad. Sci. USA 84, 3439–3443.

    Article  PubMed  CAS  Google Scholar 

  8. Hoogenboom H. R., Raus J. C., and Volckaert G. (1990). Cloning and expression of a chimeric antibody directed against the human transferrin receptor. J. Immunol. 144, 3211–3217.

    PubMed  CAS  Google Scholar 

  9. Shitara K., Kuwana Y., Nakamura K., Tokutake Y., Ohta S., Miyaji H., et al. (1993). A mouse/human chimeric anti-(ganglioside GD3) antibody with enhanced antitumor activities. Cancer Immunol. Immunother. 36, 373–380.

    Article  PubMed  CAS  Google Scholar 

  10. Krishnan I. S., Hansen H. J., Losman M. J., Goldenberg D. M., and Leung S. O. (1997). Chimerization of Mu-9: a colon-specific antigen-p antibody reactive with gastrointestinal carcinomas. Cancer 80, 2667–2674.

    Article  PubMed  CAS  Google Scholar 

  11. Hanai N., Nakamura K. and Shitara K. (2000). Recombinant antibodies against ganglioside expressed on tumor cells. Cancer Chemother. Pharmacol. 46, S13–S17.

    Article  PubMed  CAS  Google Scholar 

  12. Orlandi R., Gussow D. H., Jones P. T., and Winter G. (1989). Cloning immunoglobulin variable domains for expression by the polymerase chain reaction. Proc. Natl. Acad. Sci. USA 86, 3833–3837.

    Article  PubMed  CAS  Google Scholar 

  13. Dübel S., Breitling F., Fuchs P., Zewe M., Gotter S., Welschof M., et al. (1994). Isolation of IgG antibody Fv-DNA from various mouse and rat hybridoma cell lines using the polymerase chain reaction with a simple set of primers. J. Immunol. Methods 175, 89–95.

    Article  PubMed  Google Scholar 

  14. Liu A. Y., Robinson R. R., Murray E. D., Ledbetter J. A., Hellstrom I., and Hellstrom K. E. (1987). Production of a mouse-human chimeric monoclonal antibody to CD20 with potent Fc-dependent biologic activity. J. Immunol. 139, 3521–3526.

    PubMed  CAS  Google Scholar 

  15. Gillies S. D., Lo K. M., and Wesolowski J. (1989). High-level expression of chimeric antibodies using adapted cDNA variable region cassettes. J. Immunol. Methods 125, 191–202.

    Article  PubMed  CAS  Google Scholar 

  16. Weissenhorn W., Weiss E., Schwirzke M., Kaluza B., and Weidle U. H. (1991). Chimerization of antibodies by isolation of rearranged genomic variable regions by the polymerase chain reaction. Gene 106, 273–277.

    Article  PubMed  CAS  Google Scholar 

  17. Kabat E. A. and Wu T. T. (1971). Attempts to locate complementarity determing residues in the variable position of light and heavy chains. Ann. NY Acad. Sci. 190, 382–393.

    Article  PubMed  CAS  Google Scholar 

  18. Kabat E. A., Wu T. T., Reid-Miller M., Perry H. M., and Gottesmann K. (1987) Sequence of proteins of immunological interest. U.S. Department of Health and Human Services, U.S. Government Printing Office, Washington, DC.

    Google Scholar 

  19. Lefranc M. P. (2001). IMGT, the international ImmunoGeneTics database. Nucleic Acids Res. 29, 207–209.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Humana Press Inc.

About this protocol

Cite this protocol

Krauss, J., Förster, H.H., Uchanska-Ziegler, B., Ziegler, A. (2003). Chimerization of a Monoclonal Antibody for Treating Hodgkin's Lymphoma. In: Welschof, M., Krauss, J. (eds) Recombinant Antibodies for Cancer Therapy. Methods in Molecular Biology™, vol 207. Humana Press. https://doi.org/10.1385/1-59259-334-8:63

Download citation

  • DOI: https://doi.org/10.1385/1-59259-334-8:63

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-918-6

  • Online ISBN: 978-1-59259-334-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics