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.
Chen
Z J
ZJ
Department of Microbiology and Immunology, New York Medical College, Valhalla 10595.
Yang
H
H
Liu
C C
CC
Hirai
S
S
Ferrone
S
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000912:Antibodies, Neoplasm / Q000032:analysis / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology; D000918:Antibody Specificity; D000951:Antigens, Neoplasm; D004337:Drug Carriers / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D005620:Freund's Adjuvant / Q000494:pharmacology; D006433:Hemocyanins / Q000494:pharmacology; D006801:Humans; D007114:Immunization; D007074:Immunoglobulin G / Q000276:immunology; D000922:Immunotoxins / Q000494:pharmacology; D007457:Iodine Radioisotopes; D008297:Male; D058950:Melanoma-Specific Antigens; D051379:Mice; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000276:immunology*; D011817:Rabbits
D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D004337:Drug Carriers; D007074:Immunoglobulin G; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; C048844:anti-IgG; D005620:Freund's Adjuvant; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin