Human T-lymphocytes targeted against an established human ovarian carcinoma with a bispecific F(ab')2 antibody prolong host survival in a murine xenograft model.
A bispecific F(ab')2 fragment with anti-CD3 and antitumor specificity was used to target activated human peripheral blood lymphocytes (PBL) against OVCAR-3 human ovarian carcinoma cells growing i.p. in athymic mice. Mice were given injections of OVCAR-3 cells on day 0 and treated with i.p. injections of activated PBL coated with the [anti-CD3 (TR66) x antitumor (MOv18)] bispecific F(ab')2 on day 4, using an approximate effector:target ratio of 1:1. Treatment was evaluated for the ability either to block tumor growth at 15 days or to prolong survival of tumor-bearing mice. After 15 days, the incidence of mice with tumor growth was 20% among those given PBL coated with bispecific F(ab')2, whereas the incidence among mice untreated or treated with PBL alone or PBL with either parental antibody ranged from 80 to 94%. The mean survival time of tumor-bearing mice treated with PBL and bispecific F(ab')2 was 104 days, which was 3.5 times that of untreated mice and twice that of mice given PBL alone or PBL with either parental antibody. These results provide support for the concept that treatment of ovarian cancer patients with targeted T-cells could prove beneficial.
Mezzanzanica
D
D
Experimental Immunology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Garrido
M A
MA
Neblock
D S
DS
Daddona
P E
PE
Andrew
S M
SM
Zurawski
V R
VR
Segal
D M
DM
Wunderlich
J R
JR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D016219:Immunotherapy, Adoptive; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000401:mortality / Q000628:therapy*; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments