Inhibition of rat yolk sac tumour growth in vivo by a monoclonal antibody to the retroviral molecule P15E.
A monoclonal mouse IgG2b antibody 19F8, directed towards a determinant on the retroviral transmembranous molecule p15E, binds selectively to certain rat tumours, including all tested yolk sac tumours, one rat colon carcinoma, one spontaneous kidney carcinoma and an adenovirus-type-9-induced rat breast tumour, as tested by antibody-dependent cellular cytotoxicity (ADCC) and immunohistochemistry. Groups of rats receiving yolk sac tumour F56 isografts intraperitoneally (i.p.) or subperitoneally (s.p.) were treated with this monoclonal antibody (mAb), 19F8, inoculated twice a week in doses of 100 micrograms. Parallel control groups received analogous inoculations of an isotype-matched monoclonal antibody. A significant growth inhibitory effect was observed with 19F8. In 5/10 rats isografted i.p., tumour outgrowth was completely inhibited and in the other 5 rats the outgrowth was delayed compared to the 10 rats in the control group, which all developed tumours. All rats of the control group developed large volumes of ascites, whereas the 5 rats in the therapy group with eventual tumour outgrowth had little or no ascites. In two experiments with rats carrying subperitoneal isografts and treated with the 19F8 mAb, tumour grew out in 4/5 and 5/10 rats, though growth was delayed compared to the control groups, in which 5/5 and 9/9 rats developed tumours. The tumours grew significantly more slowly in the therapy groups compared to the controls. All rats that developed tumours in the therapy groups showed an anti-idiotypic response against mAb 19F8. The single tumour-free rat in the first experiment and 1/5 tumour-free rats in the other showed no such response. The draining lymph node cells from the tumour-free animals showed a specific proliferative response to yolk sac tumour F56 cells in a mixed lymphocyte tumour cell culture (MLTC), and the MLTC-induced cells were cytotoxic to F56 but not to the natural-killer-sensitive rat T cell lymphoma G1-Tc1. The cytotoxic cell population was more than 90% CD4+. It is concluded that the two test systems for identification of the epitope of p15E detected by mAb 19F8 correlated well in detection of the epitope in the cells (immunohistochemistry) and at the cell surface (ADCC). It is also concluded that mAb 19F8 has a growth-inhibitory effect on yolk sac tumour F56 and that, as a result of the treatment, T cells with specificity for F56 are appearing in draining lymph nodes of tumour-free animals.
Lindvall
M
M
Department of Tumor Immunology, Wallenberg Laboratory, University of Lund, Sweden.
Sjögren
H O
HO
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000920:Antibody-Dependent Cell Cytotoxicity / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D007150:Immunohistochemistry; D008649:Mesonephroma / Q000276:immunology / Q000628:therapy*; D051381:Rats; D011920:Rats, Inbred WF; D015682:Retroviridae Proteins, Oncogenic / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology; D014759:Viral Envelope Proteins / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000939:Epitopes; D015682:Retroviridae Proteins, Oncogenic; D014759:Viral Envelope Proteins