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.
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.
Ghetie
M A
MA
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235-8576.
Picker
L J
LJ
Richardson
J A
JA
Tucker
K
K
Uhr
J W
JW
Vitetta
E S
ES
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
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018941:Antigens, CD19; D000944:Antigens, Differentiation, B-Lymphocyte; D011971:Receptors, Immunologic