Immunotherapy with monoclonal antibodies directed against the immunosuppressive domain of p15E inhibits tumour growth.
Immunosuppressive retrovirus-related proteins, like p15E, are involved in tumour-associated immunosuppression. In the present study we investigated whether such proteins could be used as targets in tumour immunotherapy using MoAbs. Immunotherapy was performed in mice inoculated with the Rauscher virus-transformed myeloid cell line RMB-1. RMB-1 cells express retroviral antigens at their cell surface. In order to obtain constant serum titres of MoAbs over a prolonged period of time during therapy, anti-p15E antibody-producing hybridoma cells were encapsulated in alginate and injected intraperitoneally in tumour-bearing mice. Using this technique, serum antibody titres of 50-100 micrograms/ml were obtained, which remained constant over a period of at least 3 weeks. Therapy experiments were performed using anti-p15E antibodies 19F8, which recognizes both cell surface-associated as well as circulating p15E, and ER-IS5, which did not react with surface-bound p15E beyond background, but which neutralizes circulating p15E. Inoculation of alginates containing anti-p15E hybridoma cell lines in RMB-1 tumour-bearing mice showed inhibition of tumour cell growth. In survival experiments, 19F8 cured eight of 23 tumour-bearing mice. The p15E neutralizing antibody ER-IS5 caused a significant longer survival, but therapy with this MoAb alone was not sufficient to cure the animals of the RMB-1 tumour.
Department of Immunology, Erasmus University, Rotterdam, The Netherlands.
M S
MS
Lang
E
E
Hovenkamp
H F
HF
Savelkoul
P
P
Knegt
W
W
Van Ewijk
D000464:Alginates / Q000008:administration & dosage; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D005260:Female; D006825:Hybridomas / Q000276:immunology; D007108:Immune Tolerance; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009363:Neoplasm Proteins; D009374:Neoplasms, Experimental / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D012191:Retroviridae Proteins / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
D000464:Alginates; D000911:Antibodies, Monoclonal; D009363:Neoplasm Proteins; D012191:Retroviridae Proteins; D014759:Viral Envelope Proteins; C489582:retroviral p15E-related protein, mouse