Modulation by adjuvants and carriers of the immunogenicity in xenogeneic hosts of mouse anti-idiotypic monoclonal antibody MK2-23, an internal image of human high molecular weight-melanoma associated antigen.
The mouse anti-idiotypic monoclonal antibody (mAb) MK2-23 recognizes an idiotope in the antigen-combining site of the immunizing anti-human high-molecular-weight melanoma-associated antigen (HMW-MAA) mAb 763.74. Administration with an adjuvant of mAb MK2-23 conjugated to a carrier has been shown to induce anti-HMW-MAA antibodies both in syngeneic hosts and in patients with malignant melanoma. Adjuvant and carrier are required for the induction of anti-HMW-MAA immunity in BALB/c mice immunized with mAb MK2-23. Whether both adjuvant and carrier are required also in patients with malignant melanoma is not known and cannot be deduced from results obtained in a syngeneic animal model system. Therefore the present study has evaluated for the first time the effect of a carrier and an adjuvant on the immunogenicity of mAb MK2-23 in a xenogeneic host. Rabbits were selected for this purpose, since they have a constitutive expression of HMW-MAA in their normal tissues with a distribution similar to that in humans. The combined use of an adjuvant and a carrier enhances the immunogenicity of mAb MK2-23 in rabbits markedly more than each of them individually. Specifically, all the rabbits immunized with mAb MK2-23 conjugated to keyhole limpet hemocyanin (KLH) and mixed with Freund's adjuvant (FA) produced antibodies which were shown with serological and immunochemical assays to be specific for HMW-MAA and to be both IgG and IgM. In contrast anti-HMW-MAA antibodies were detected in only one of the 3 rabbits immunized with mAb MK2-23 mixed with FA and were not detected in the rabbits immunized with mAb MK2-23 conjugated to KLH or with mAb MK2-23 without KLH and FA. These results indicate that active specific immunotherapy with mAb MK2-23 in patients with malignant melanoma is likely to benefit from the use of a carrier and an adjuvant, provide additional evidence that mAb MK2-23 bears the internal image of HMW-MAA, and suggest that the immune response elicited by mAb MK2-23 is T-cell dependent.