Efficient inhibition of human B-cell lymphoma xenografts with an anti-CD20 x anti-CD3 bispecific diabody.
Bispecific antibodies have been exploited both as cancer immunodiagnostics and as cancer therapeutics, and have shown promise in several clinical trials in cancer imaging and therapy. A number of bispecific antibodies against B-cell markers have been shown to be effective in vitro in mediating tumor cell lysis and in vivo in inhibiting tumor growth in animal models. We have constructed a bispecific diabody from the variable genes encoding two hybridoma-derived monoclonal antibodies directed against human CD20 on B cells and CD3 on T cells. The anti-CD20 x anti-CD3 diabody was expressed in a single Escherichia coli host and purified by a one-step affinity chromatography. The bispecific diabody bound as efficiently to both CD20- and CD3-positive cells as the respective parental antibodies, and was capable of cross-linking CD20-positive tumor cells and human T lymphocytes as shown by cellular rosetting. The diabody effectively lysed human B-lymphoma cells in the presence of T-enriched human peripheral blood lymphocytes (PBL). Further, when combined with human PBL and interleukin-2, the diabody significantly prolonged the survival of nude mice inoculated with human B-lymphoma cells. Taken together, our results suggest that an anti-CD20 x anti-CD3 diabody may have significant clinical application in the treatment of human CD20-positive B-cell malignancies.
Xiong
Dongsheng
D
State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, People's Republic of China.
Xu
Yuanfu
Y
Liu
Hanzhi
H
Peng
Hui
H
Shao
Xiaofeng
X
Lai
Zenzu
Z
Fan
Dongmei
D
Yang
Min
M
Han
Junling
J
Xie
Yong
Y
Yang
Chunzheng
C
Zhu
Zhenping
Z
D000818:Animals; D018033:Antibodies, Bispecific / Q000627:therapeutic use*; D018951:Antigens, CD20 / Q000276:immunology*; D001666:Binding Sites, Antibody; D017252:CD3 Complex / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D005822:Genetic Vectors; D006801:Humans; D019169:Jurkat Cells; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000627:therapeutic use; D015996:Survival Rate; D014183:Transplantation, Heterologous
D018033:Antibodies, Bispecific; D018951:Antigens, CD20; D017252:CD3 Complex; D011994:Recombinant Proteins