title: Anti-CD19 inhibits the growth of human B-cell tumor lines in vitro and of Daudi cells in SCID mice by inducing cell cycle arrest.
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 x 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.
authors.affiliation: Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235-8576.
authors.forename: M A
authors.initials: MA
authors.lastname: Ghetie
authors.forename: L J
authors.initials: LJ
authors.lastname: Picker
authors.forename: J A
authors.initials: JA
authors.lastname: Richardson
authors.forename: K
authors.initials: K
authors.lastname: Tucker
authors.forename: J W
authors.initials: JW
authors.lastname: Uhr
authors.forename: E S
authors.initials: ES
authors.lastname: Vitetta
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000502:physiology*; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology*; D002453:Cell Cycle; D002460:Cell Line; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D016513:Mice, SCID; D011940:Receptor Aggregation; D011971:Receptors, Immunologic / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D011971:Receptors, Immunologic