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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 sites.
Cancer Res. 1991 Nov 01; 51(21):5876-80.CR

Abstract

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 was 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.

Authors+Show Affiliations

Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

1933855

Citation

Ghetie, M A., et al. "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 Sites." Cancer Research, vol. 51, no. 21, 1991, pp. 5876-80.
Ghetie MA, Richardson J, Tucker T, et al. 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 sites. Cancer Res. 1991;51(21):5876-80.
Ghetie, M. A., Richardson, J., Tucker, T., Jones, D., Uhr, J. W., & Vitetta, E. S. (1991). 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 sites. Cancer Research, 51(21), 5876-80.
Ghetie MA, et al. 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 Sites. Cancer Res. 1991 Nov 1;51(21):5876-80. PubMed PMID: 1933855.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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 sites. AU - Ghetie,M A, AU - Richardson,J, AU - Tucker,T, AU - Jones,D, AU - Uhr,J W, AU - Vitetta,E S, PY - 1991/11/1/pubmed PY - 1991/11/1/medline PY - 1991/11/1/entrez SP - 5876 EP - 80 JF - Cancer research JO - Cancer Res VL - 51 IS - 21 N2 - 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 was 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. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/1933855/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_sites_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=1933855 DB - PRIME DP - Unbound Medicine ER -