Effect of hapten plus antihapten-tumor serum treatment on established rat fibrosarcoma.

ments has been only an occasional inhibition of the devel opment of transplanted tumor cells (22). Although the regression of established tumors induced by Moloney virus (11, 14), polyoma virus (5, 6), and reticuloendotheliosis virus (16) has been reported , such successful results have been rare. Many factors which will affect successful regres sion of tumor in serotherapy have@been suggested by Rosenberg and Terry (22) in their recent review. However, the fact that these rare examples of regression occurred in highly immunogeneic tumors (11, 14, 16), as evidenced by their spontaneous regression, indicates the importance of strong antigenicity oftargettumor for a successful outcome with serotherapy. The intrinsically weak antigenicity of tumor may be ineffective not only in inducing an immune response of the host but also as a potential target for selective immunological attack. In an attempt to overcome the problems due to the weak antigenicity of tumor, Burke et a!. (8, 9) used i.v. PhM3 as a hapten to modify the tumor antigens and followed with an i.v. injection of antibody directed against the PhM conju gated with the target tumor cells. This system proved efficient in causing specific destruction of tumor tissue. However,a high incidence of anaphylaxis-like reaction was observed. Since i.v. administered PhM rapidly conjugates with plasma proteins (23), PhM-conjugated proteins might be created by the i.v. PhM injection and evoke an anaphy lactic reaction with the subsequently injected PhM-specific antibody. Thus, we decided to avoid the i.v. use of PhM. We previously confirmed the haptenic activity of PhM by comparative studies of allogeneic and xenogeneic antisera produced with PhM-conjugated extracts of rat or human tumors (1). The antiserum induced with PhM-conjugated extract of allogeneic rat tumor produced antibodies inde pendently specific to PhM, PhM-tumor conjugate, and tu mor. In our model, an i.t. injection of PhM to modify the antigenicity of proteins in tumor tissue was followed by an i.v. administration of antiserum produced against PhM conjugated extract of tumor. This type of antiserum was used to take advantage of the effect of carrier (tumor)specific antibody in addition to the hapten-specific anti body. A single treatment by this system completely re gressed established Walker tumor in allogeneic rats and cured most of the animals (2). The results of this study indicated that the regression was caused by neither PhM alone nor antiserum alone. Additional repeated administra tions of high doses of hydrocortisone eliminated the regres