Effect of local immunotherapy of syngeneic rat fibrosarcoma with hapten and antihapten-tumor serum upon nonlocally treated tumor.

Previously, we produced complete regression of allogeneic and syngeneic rat tumors by in situ tumor modification with a hapten, L-phenylalanine mustard (PhM), followed by i.v. admin istration of an antiserum developed against PhM-tumor extract conjugate. To evaluate the effect of this local treatment on untreated tumors, only one of two syngeneic methylcholanthrene-induced rat fibrosarcomas transplanted to both thighs of Lewis rats was treated. The syngeneic antiserum produced against the con jugate of PhM and fibrosarcoma extract contained PhM-spe cific antibody and a barely detectable level of antibody specific to the conjugate. All of the paired tumors in untreated rats progressively grew and killed the hosts. Intnatumonal(i.t.) injection of PhM only to the left tumor followed by i.v. administration of the antiserum produced uniform regression of all tumors, with disappearance of both treated (6 of 11 animals) and untreated (9 of 11 animals) tumors and prolonged survival time. Of the tumors which dis appeared, three treated and five untreated tumors did not recur, and two rats were cured. The substitution of antiserum with normal serum or the substitution of the i.t. injection of PhM with s.c. PhM injection resulted in a significantly lower effect on both paired tumors, and there were no cures, indicating that the combination of i.t. injection of PhM and antiserum is impor tant for successful tumor regression. Regression of the uninjected tumor was significantly greater in the PhM i.t.-antiserum group than in any other PhM-injected group. This difference cannot be explained by a systemic effect of PhM. In addition, the effect of PhM i.t.-antisenum on the uninjected right side tumor was markedly reduced by the excision of PhM-injected left side tumor. These results suggest that treated and retained regressing tumor tissue may be beneficial for the regression of the uninjected tumor. Interestingly, each pair of tumors synchronously changed its volume with a highly significant positive linear correlation, regardless of treatment modality, differences in tumor growth patterns, or differences in initial sizes of the paired tumors. In the PhM i.t.-antiserum group, this correlation seems to suggest the induction of systemic effects by the local treatment.