Anti-CD19 nhibits the growth of human B-cell tumor lines in vitro and of Daudi cells in SCID mice by inducing cell cycle arrest

Maria Ana Ghetie, Louis J. Picker, James A. Richardson, Karsten Tucker, Jonathan W. Uhr, Ellen S. Vitetta

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Abstract

In this report, we extend our previous findings that IgG or F(ab′)2 fragments of HD37 anti-CD19 antibody (Ab) in combination with the immunotoxin (IT), RFB4-anti-CD22-deglycosylated ricin A chain (dgA) (but neither reagent alone), prolonged the survival of SCID mice with disseminated human Daudi lymphoma (SCID/Daudi mice) to 1 year at which time they still remained tumor-free. We explored the mechanisms by which the HD37 Ab exerts antitumor activity in vivo by studying its activity in vitro. We found that it has antiproliferative activity (IC50 = 5.2 - 9.8 × 10-7 mol/L) on three CD19+ Burkitt's lymphoma cell lines (Daudi, Raji, and Namalwa) but not on a weakly CD19-positive (CD19lo) pre-B cell tumor (Nalm-6). The inhibitory effect was manifested by cell cycle arrest, but not apoptosis. Results using three additional anti-CD19 Abs, suggest that the affinity of the antibody and possibly the epitope which it recognizes may effect its capacity to transmit a signal that induces cell cycle arrest. Hence, therapeutically useful Abs may exert anti-tumor activity by a variety of mechanisms, each of which should be evaluated before undertaking clinical trials in humans.

Original languageEnglish (US)
Pages (from-to)1329-1336
Number of pages8
JournalBlood
Volume83
Issue number5
StatePublished - Mar 1 1994

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SCID Mice
Cell Cycle Checkpoints
Tumors
B-Lymphocytes
Cells
Cell Line
Growth
Ricin
Antibodies
Immunotoxins
Neoplasms
Antibody Affinity
B-Lymphoid Precursor Cells
Burkitt Lymphoma
Inhibitory Concentration 50
Epitopes
Anti-Idiotypic Antibodies
Lymphoma
Immunoglobulin G
Clinical Trials

ASJC Scopus subject areas

  • Hematology

Cite this

Anti-CD19 nhibits the growth of human B-cell tumor lines in vitro and of Daudi cells in SCID mice by inducing cell cycle arrest. / Ghetie, Maria Ana; Picker, Louis J.; Richardson, James A.; Tucker, Karsten; Uhr, Jonathan W.; Vitetta, Ellen S.

In: Blood, Vol. 83, No. 5, 01.03.1994, p. 1329-1336.

Research output: Contribution to journalArticle

Ghetie, Maria Ana ; Picker, Louis J. ; Richardson, James A. ; Tucker, Karsten ; Uhr, Jonathan W. ; Vitetta, Ellen S. / Anti-CD19 nhibits the growth of human B-cell tumor lines in vitro and of Daudi cells in SCID mice by inducing cell cycle arrest. In: Blood. 1994 ; Vol. 83, No. 5. pp. 1329-1336.
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