Susceptibility of B-cell lymphoma to human antibodies encoded by the V4-34 gene.
Our previous studies have shown that mAbs derived from the human V4-34 gene bind and kill human B-lymphocytes via membrane disruption. This study demonstrates the cytotoxicity of two V4-34 encoded mAbs, 216 and Z2D2, towards human B-cell lymphoma. In vitro, 216 and Z2D2 are cytotoxic to a variety of B-cell lymphomas obtained from patient biopsies. In vivo, increased survival was observed with both mAbs in a lymphoma model developed in scid mice with human B-cell line Nalm-6. Studies in mice show that these mAbs are well tolerated with minimum side effects. Since 216 and Z2D2 show increased toxicity towards cycling cells, V4-34 mAb-based therapy can be additive with drugs that block cell-cycle progression. Stem cells that are V4-34 mAb ligand negative would not be depleted. Together, these studies recommend an evaluation of the two completely human mAbs in a phase I trial for B-cell lymphoma.
Bhat
N M
NM
Department of Gynecology and Obstetrics, Stanford University Medical Center, Stanford, CA 94305-5317, USA. nbhat@stanford.edu
Bieber
M M
MM
Young
L W
LW
Teng
N N
NN
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D005803:Genes, Immunoglobulin; D006801:Humans; D016393:Lymphoma, B-Cell / Q000188:drug therapy*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D015996:Survival Rate; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000637:transplantation
D000911:Antibodies, Monoclonal