We previously demonstrated the haptenic activity of l-phenylalanine mustard (PhM) and that modification of tumor in situ with this hapten, followed by passive immunization with antiserum produced against PhM-conjugated tumor extract, completely regressed allogeneic rat tumor.
To determine the influence of histocompatibility antigens on the efficacy of this therapy system, syngeneic fibrosarcoma (MC1) in Lewis rat and syngeneic or xenogeneic antiserum produced against PhM-conjugated MC1 extract were used. Both antisera contained mainly PhM-specific antibody. In addition, a weak PhM-MC1 conjugate-specific antibody and a barely detectable MC1-specific antibody were found in the syngeneic antiserum. A very low titer of MC1-specific antibody was also found in the xenogeneic antiserum.
Rats with MC1 were treated using syngeneic antiserum as follows: (a) intratumoral (i.t.) injection with PhM in phosphate buffer followed by an i.v. injection of antiserum; (b) PhM (i.t.) plus normal serum (i.v.); (c) buffer (i.t.) plus antiserum (i.v.); and (d) buffer (i.t.) plus normal serum (i.v.). Tumor disappearance (5 of 11) occurred only in the PhM-antiserum group, with one rat cured. The mean survival time of this group was significantly longer than that for any of the other groups. Rabbit antiserum absorbed with rat normal tissue was then substituted, since a xenogeneic antiserum might have more clinical relevancy. Four groups of rats with MC1 were treated as noted above. A fifth group received no treatment. Despite large initial tumors, all nine rats in the PhM-antiserum group uniformly showed a significant reduction of tumor volume compared with any other group and had a longer survival time.
In another study, i.v. injected syngeneic antiserum produced a PhM-specific reaction against intracutaneously injected PhM or PhM-conjugated antigens, indicating that an immunological mechanism may be active in the treatment described above. The results indicate that PhM-antiserum treatment can produce complete regression of an established tumor under appropriate conditions. The effect is due to neither PhM alone nor antiserum alone and appears to be reproducible regardless of the type of tumor or the source of antiserum.
This work was supported by Contract No-1-CB-43967 from the National Cancer Institute.