A bispecific antibody prolongs survival in mice bearing lung metastases of syngeneic mammary adenocarcinoma.
In the present study we tested whether T cells retargeted with a bispecific antibody (bsAb) could block the growth of lung metastases of syngeneic mammary adenocarcinoma in immunocompetent mice. BALB/c mice were injected i.v. with tumor and i.p. with a genetically engineered bispecific F(ab')2 [bs(Fab')2] having specificity for murine CD3 epsilon chain and for the gp52 mouse mammary tumor viral glycoprotein, which is expressed on the tumor cells. The bs(Fab')2 was physically stable in blood and serum, was removed from the body with a half-time of 12-15 h, and accumulated in lymphoid tissue where it bound to T cells. We show that treatment of tumor bearing mice with the bs(Fab')2 significantly prolonged their survival relative to untreated controls. Two other genetically engineered bs(Fab')2s having specificity for murine CD3 epsilon chain and irrelevant antigens did not inhibit tumor growth. In addition, survival was not affected by bsAb therapy using a variant tumor cell line that expressed low levels of the gp52 target antigen. Inhibition of tumor growth was even more evident by histologic analysis. Treatment with the relevant bs(Fab')2 resulted in a marked reduction of tumor burden in lung sections taken on days 7, 9 and 11. This is the first report demonstrating that a bsAb can inhibit the growth of syngeneic solid tumor metastases in mice without addition of T cell activators.
Bakács
T
T
Experimental Immunology Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Lee
J
J
Moreno
M B
MB
Zacharchuk
C M
CM
Cole
M S
MS
Tso
J Y
JY
Paik
C H
CH
Ward
J M
JM
Segal
D M
DM
D000230:Adenocarcinoma / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D000818:Animals; D018033:Antibodies, Bispecific / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000951:Antigens, Neoplasm / Q000276:immunology; D000957:Antigens, Viral, Tumor / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary* / Q000628:therapy*; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology
D018033:Antibodies, Bispecific; D000951:Antigens, Neoplasm; D000957:Antigens, Viral, Tumor; D017252:CD3 Complex; D006023:Glycoproteins; D007140:Immunoglobulin Fab Fragments; D014759:Viral Envelope Proteins; C040612:glycoprotein 52 antigen, Mouse mammary tumor virus