Bispecific antibodies and retargeted cellular cytotoxicity: novel approaches to cancer therapy.
We have used a relatively new technology to increase the number of human lymphocytes that will react with human ovarian carcinoma cells. This technology, often called "retargeting of the immune system," can temporarily redirect the activity of immune cells that were originally committed to react with foreign substances other than cancer cells. In the example presented here, the antitumor effects of retargeted human T lymphocytes, collected from normal donors, were tested in immunodeficient mice with a human ovarian carcinoma line growing intraperitoneally. We retargeted T cells in vitro with a bispecific antibody that reacted with the T cell receptor complex and with a cell-surface antigen expressed by the ovarian carcinoma cells. Retargeted lymphocytes, injected intraperitoneally into mice 4 days after intraperitoneal injection of the tumor cells, impeded tumor growth and doubled the host survival time. These findings provide support for the concept that treatment of ovarian cancer patients with retargeted T cells could prove beneficial.
Wunderlich
J R
JR
Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, MD 20892.
Mezzanzanica
D
D
Garrido
M A
MA
Neblock
D S
DS
Daddona
P E
PE
Andrew
S M
SM
Zurawski
V R
VR
Canevari
S
S
Colnaghi
M I
MI
Segal
D M
DM
D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D005260:Female; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000401:mortality / Q000628:therapy*; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000906:Antibodies; D000911:Antibodies, Monoclonal