This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ghetie, M.-A. Articles by Vitetta, E. S. Search for Related Content PubMed PubMed Citation Articles by Ghetie, M.-A. Articles by Vitetta, E. S.

Antitumor Activity of Fab' and IgG-anti-CD22 Immunotoxins in Disseminated Human B Lymphoma Grown in Mice with Severe Combined Immunodeficiency Disease: Effect on Tumor Cells in Extranodal Sites¹

Departments of Microbiology [M-A. G., T. T., D. J., J. W. U., E. S. V.] and Pathology [J. R.] and Division of Comparative Medicine [J. R.] and the Cancer Immunobiology Center [E. S. V.], University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75235

The antitumor effects of two anti-CD22 ricin A chain-containing immunotoxin (IT) constructs were compared in mice with severe combined immunodeficiency disease with human Daudi cell tumors (SCID-Daudi mice). SCID-Daudi mice develop disseminated lymphoma that clinically resembles African Burkitt's lymphoma, i.e., extranodal disease including infiltration of the vertebral column and spinal canal. In the absence of treatment, the mean survival time of SCID-Daudi mice was 45.9 ± 4.3 days. The mice were given injections of a dose of IT equal to 40% of the 50% lethal dose. The ITs consisted of either IgG or Fab' fragments of mouse anti-CD22 antibody coupled to deglycosylated ricin A chain (dgA). Both ITs were potent and specific and inhibited protein synthesis in Daudi cells in vitro by 50% at concentrations of 1.2 x 10^–12 (IgG-dgA) and 1.3 x 10^–11 M (Fab'-dgA). When administered to mice beginning 1 day after inoculation with tumor cells, both ITs extended the mean survival time, to 87.2 ± 18.9 days (IgG-dgA) or 57.9 ± 3.8 days (Fab'-dgA). The latter represented the killing of 2 logs of Daudi cells, and the former 4 logs. IgG antibody alone killed 1 log of tumor cells. The IgG-dgA had an antitumor effect even when administered 20–23 days after tumor inoculation. Gross and histological examinations of IT-treated tumor-bearing mice showed a marked decrease in the number and size of neoplastic foci in both lymphoid organs and extranodal sites.

¹ Supported by NIH Grants CA42228, CA28149, and RR00890, Texas Technology Grant 18512, a grant from the Welch Foundation I-947, and a grant from the Overton Foundation.

² To whom requests for reprints should be addressed, at Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75235.

Received 6/ 3/91. Accepted 8/20/91.

This article has been cited by other articles:

				J. Carnahan, P. Wang, R. Kendall, C. Chen, S. Hu, T. Boone, T. Juan, J. Talvenheimo, S. Montestruque, J. Sun, et al. Epratuzumab, a Humanized Monoclonal Antibody Targeting CD22: Characterization of in Vitro Properties Clin. Cancer Res., September 1, 2003; 9(10): 3982S - 3990. [Abstract] [Full Text] [PDF]

				D. L. Newton, H. J. Hansen, S. M. Mikulski, D. M. Goldenberg, and S. M. Rybak Potent and specific antitumor effects of an anti-CD22-targeted cytotoxic ribonuclease: potential for the treatment of non-Hodgkin lymphoma Blood, January 15, 2001; 97(2): 528 - 535. [Abstract] [Full Text] [PDF]

				R. J. Kreitman, I. Margulies, M. Stetler-Stevenson, Q.-C. Wang, D. J. P. FitzGerald, and I. Pastan Cytotoxic Activity of Disulfide-stabilized Recombinant Immunotoxin RFB4(dsFv)-PE38 (BL22) toward Fresh Malignant Cells from Patients with B-Cell Leukemias Clin. Cancer Res., April 1, 2000; 6(4): 1476 - 1487. [Abstract] [Full Text]

				B.-R. Wei, M.-A. Ghetie, and E. S. Vitetta The Combined Use of an Immunotoxin and a Radioimmunoconjugate to Treat Disseminated Human B-Cell Lymphoma in Immunodeficient Mice Clin. Cancer Res., February 1, 2000; 6(2): 631 - 642. [Abstract] [Full Text]

				E. Mansfield, P. Amlot, I. Pastan, and D. J. FitzGerald Recombinant RFB4 Immunotoxins Exhibit Potent Cytotoxic Activity for CD22-Bearing Cells and Tumors Blood, September 1, 1997; 90(5): 2020 - 2026. [Abstract] [Full Text] [PDF]