Cure of xenografted human tumors by bispecific monoclonal antibodies and human T cells.
Tumor immunotherapy should increase both the number of T cells that kill the tumor and the likelihood that those cells are activated at the tumor site. Bispecific monoclonal antibodies (Bi-mAbs) were designed that bound to a Hodgkin's tumor-associated antigen (CD30) on the tumor and to either CD3 or CD28 on the T cell. Immunodeficient mice were cured of established human tumors when mice were treated with both the CD3-CD30 and the CD28-CD30 Bi-mAbs and then given human peripheral blood lymphocytes that had been incubated with the CD3-CD30 Bi-mAb and cells that expressed CD30. The enrichment of human T cells within the tumor and the fact that established tumors can be cured may indicate in situ activation of both the T cell receptor and the costimulatory pathway.
Renner
C
C
Medizinische Klinik und Poliklinik, Universität des Saarlandes, Homburg, Germany.
Jung
W
W
Sahin
U
U
Denfeld
R
R
Pohl
C
C
Trümper
L
L
Hartmann
F
F
Diehl
V
V
van Lier
R
R
Pfreundschuh
M
M
D000818:Animals; D018033:Antibodies, Bispecific / Q000276:immunology / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal; D018106:CD28 Antigens / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology*; D006689:Hodgkin Disease / Q000276:immunology / Q000628:therapy*; D006801:Humans; D017730:Ki-1 Antigen / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014183:Transplantation, Heterologous
D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D017730:Ki-1 Antigen; D011948:Receptors, Antigen, T-Cell