Abstract
Antibodies can be conjugated to effector molecules to derive targeted therapeutics with properties such as cell-specific cytotoxicity. The murine anti-CD22 antibody RFB4 linked to a member of the ribonuclease A superfamily, Onconase (Onc), becomes a potential drug candidate for non-Hodgkin’s lymphoma. Onc is currently in Phase III clinical trials for unresectable malignant mesothelioma but conjugation to RFB4 considerably enhances its specificity for CD22+ lymphomas. RFB4-targeted Onc is effective in preclinical models, causes little non-specific toxicities in mice, and has favorable formulation properties. Derivatization and conjugation of RFB4 and Onc have been optimized.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Kohler, G., and Milstein, C. (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256, 495–497.
Carter, P. J. (2006) Potent antibody therapeutics by design. Nature Rev. Immunol. 6, 343–357.
Hamann, P. R., Hinman, L. M., Hollander, I., Beyer, C. F., Lindh, D., Holcomb, R., et al. (2002) Gemtuzumab ozogamicin, a potent and selective anti-CD33 antibody–calicheamicin conjugate for treatment of acute myeloid leukemia. Bioconjug. Chem. 13 (1), 47–58.
Pastan, I., Hassan, R., Fitzgerald, D. J., and Kreitman, R. J. (2007) Immunotoxin treatment of cancer. Annu. Rev. Med. 58, 221–237.
Wong, L., Suh, D. Y., and Frankel, A. E. (2005) Toxin conjugate therapy of cancer. Semin. Oncol. 32, 591–595.
Rybak, S. M., and Newton, D. L. (2007) Immunotoxins and beyond: Targeted RNases. In: Dubel, S. (ed). Handbook of Therapeutic Antibodies, Wiley-VCH, Weinheim.
Rybak, S. M., Saxena, S. K., Ackerman, E. J., and Youle, R. J. (1991) Cytotoxic potential of ribonuclease and ribonuclease hybrid proteins. J. Biol. Chem. 266, 21202–21207.
Rybak, S. M., Newton, D. L., Mikulski, S. M., Viera, A., and Youle, R. J. (1993) Cytotoxic Onconase and ribonuclease A chimeras: Comparison and in vitro characterization. Drug Delivery 1, 3–10.
Newton, D. L., Ilercil, O., Laske, D. W., Oldfield, E., Rybak, S. M., and Youle, R. J. (1992) Cytotoxic ribonuclease chimeras: Targeted tumoricidal activity in vitro and in vivo. J. Biol. Chem. 267, 19572–19578.
Kelm, S., Pelz, A., Schauer, R., Filbin, M. T., Tang, S., deBellard, M.-E., et al. (1994) Sialoadhesin, myelin-associate glycoprotein and CD22 define a new family of sialic acid-dependent adhesion molecules of the immunoglobulin superfamily. Curr. Biol. 4, 965–972.
Kreitman, R. J., Squires, D. R., Stetler-Stevenson, M., Noel, P., fitzGerald, D. J. P., Wilson, W. H., et al. (2005) Phase I trial of recombinant immunotoxin RFB4(dsFv)-PAE38 (BL22) in patients with B-cell malignancies. J. Clin. Onc. 23, 6719–6729.
Darzynkiewicz, Z., Carter, S. P., Mikulski, S. M., Ardelt, W. J., and Shogen, K. (1988) Cytostatic and cytotoxic effects of Pannon (P-30 protein) a novel anti-cancer agent. Cell Tissue Kinet. 21, 169–182.
Mikulski, S. M., Ardelt, W., Shogen, K., Bernstein, E. H., and Menduke, H. (1990) Striking increase of survival of mice bearing M109 Madison carcinoma treated with a novel protein from amphibian embryos. J. Natl. Cancer Inst. 82, 151–153.
Lin, J. J., Newton, D. L., Mikulski, S. M., Kung, H. F., Youle, R. J., and Rybak, S. M. (1994) Characterization of the mechanism of cellular and cell free protein synthesis inhibition by an anti-tumor ribonuclease. Biochem. Biophys. Res. Commun. 204, 156–162.
Iordanov, M. S., Ryabinina, O. P., Wong, J., Dinh, T.-H., Newton, D. L., Rybak, S. M., et al. (2000) Molecular determinants of programmed cell death induced by the cytotoxic ribonuclease Onconase: evidence for cytotoxic mechanisms different from inhibition of protein synthesis. Cancer Res. 60, 1983–1994.
Saxena, S., Sirdeshmukh, R., Ardelt, W., Mikulski, S. M., Shogen, k., and Youle, R. J. (2002) Entry into cells and selective degradation of tRNAs by a cytotoxic member of the RNase A family. J. Biol. Chem. 277, 15142–15146.
Costanzi, J., Sidransky, D., Navon, A., and Goldsweig, H. (2005) Ribonucleases as a novel pro-apoptotic anticancer strategy: review of the preclinical and clinical data for ranpirnase. Cancer Invest. 23, 643–650.
Ardelt, B., Ardelt, W., and Darzynkiewicz, Z. (2003) Cytotoxic ribonucleases and RNA interference (RNAi). Cell Cycle 2, 22–24.
Mikulski, S., Costanzi, J., Vogelzang, N., McCachres, S., Taub, R., Chun, H., et al. (2002) Phase II trial of a single weekly intravenous dose of ranpirnase in patients with unresectable malignant mesothelioma. J. Clin. Oncol. 20, 274–281.
Ardelt, W., Mikulski, S. M., and Shogen, K. (1991) Amino acid sequence of an anti-tumor protein from Rana pipiens oocytes and early embryos. J. Biol. Chem. 266, 245–251.
Newton, D. L., Walbridge, S., Mikulski, S. M., Ardelt, W., Shogen, K., Ackerman, S. J., et al. (1994) Toxicity of an anti-tumor ribonuclease to Purkinje neurons. J. Neurosci. 14, 538–544.
Messmann, R. A., Vitetta, E. S., Headlee, D., Senderowicz, A. M., Figg, W. D., Schindler, J., et al. (2000) A phase 1 study of combination therapy with immunotoxins IgG-HD37-deglycosylated Ricin A chain (dgA) and IgG-RFB4-dgA (combotox) in patients with refractory CD19 (+), CD22 (–) B cell lymphoma. Clin. Cancer Res. 6, 1302–1313.
Ghetie, M. A., Richardson, J., Tucker, T., Jones, D., Uhr, J. W., and Vitetta, E. S. (1990) Disseminated or localized growth of a human B-cell tumor (Daudi) in SCID mice. Int. J. Cancer 45, 481–485.
Acknowledgments
The technical support of Dale Ruby and Miriam Hursey is gratefully acknowledged. We thank Dr. Ellen Vitetta for making the original RFB4 antibody clone available and Kuslima Shogen for the Onc. Our sincere thanks to Drs. Stephen Creekmore, Toby Hecht, and Edward A. Sausville for many helpful discussions. This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. NO1-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This research was supported (in part) by the Developmental Therapeutics Program in the Division of Cancer Treatment and Diagnosis of the National Cancer Institute.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Humana Press, a part of Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Newton, D.L., Stockwin, L.H., Rybak, S.M. (2009). Anti-CD22 Onconase: Preparation and Characterization. In: Dimitrov, A. (eds) Therapeutic Antibodies. Methods in Molecular Biology™, vol 525. Humana Press. https://doi.org/10.1007/978-1-59745-554-1_22
Download citation
DOI: https://doi.org/10.1007/978-1-59745-554-1_22
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-934115-92-3
Online ISBN: 978-1-59745-554-1
eBook Packages: Springer Protocols