PRECLINICAL EVALUATION IN NONHUMAN-PRIMATES OF MURINE MONOCLONAL ANTIIDIOTYPE ANTIBODY THAT MIMICS THE DISIALOGANGLIOSIDE GD2

The antiganglioside GD2 monoclonal antibody 14G2a (Ab1) served as an i mmunogen to generate the anti-idiotype (anti-Id) 1A7 (IgG1, kappa), wh ich mimics GD2 both antigenically and biologically, Anti-Id 1A7 induce d anti-GD2 antibodies in mice and rabbits. In this preclinical study, a pair of cynomolgus monkeys, immunized with 1A7 that had been mixed w ith QS-21 adjuvant, produced anti-anti-Id antibodies (Ab3), which reac ted with the GD2-positive melanoma cell line M21/P6 cells but not with GD2-negative LS174-T cells. The Ab3 shared Ids with mAb 14G2a (Ab1), as demonstrated by their ability to inhibit binding of 1A7 to this Ab1 . The Ab3 bound specifically to purified GD2 antigen and competed with the Ab1 14G2a in binding to a GD2-positive melanoma cell line or to p urified GD2, suggesting that Ab1 and Ab3 may bind to the same epitope and may behave as an Ab1-like antibody (Ab1'). The isotype of the GD2- specific antibodies was mostly IgG in nature. The specificity of the a ntibodies for GD2 was further confirmed by dot blot analysis. These an tisera also specifically lysed GD2-positive target cells in an antibod y-dependent cellular cytotoxicity assay. The induction of anti-GD2 res ponses in monkeys did not cause any apparent side effects, despite the fact that GD2 antigen is expressed by many normal tissues of these an imals. Taken together, these results suggest that anti-Id 1A7 can indu ce GD2-specific antibodies in nonhuman primates and can thus serve as a potential network antigen for triggering active anti-GD2 antibodies in patients with GD2-positive neuroectodermal tumors.