Preclinical evaluation in nonhuman primates of murine monoclonal anti-idiotype antibody that mimics the disialoganglioside GD2.
The antiganglioside GD2 monoclonal antibody 14G2a (Ab1) served as an immunogen to generate the anti-idiotype (anti-Id) 1A7 (IgG1,kappa), which mimics GD2 both antigenically and biologically. Anti-Id 1A7 induced anti-GD2 antibodies in mice and rabbits. In this preclinical study, a pair of cynomolgus monkeys, immunized with 1A7 that had been mixed with QS-21 adjuvant, produced anti-anti-Id antibodies (Ab3), which reacted 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 purified 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 antibodies for GD2 was further confirmed by dot blot analysis. These antisera also specifically lysed GD2-positive target cells in an antibody-dependent cellular cytotoxicity assay. The induction of anti-GD2 responses in monkeys did not cause any apparent side effects, despite the fact that GD2 antigen is expressed by many normal tissues of these animals. Taken together, these results suggest that anti-Id 1A7 can induce 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.
Sen
G
G
Department of Medicine and Markey Cancer Center, University of Kentucky, Lexington, Kentucky 40536, USA.
Chakraborty
M
M
Foon
K A
KA
Reisfeld
R A
RA
Bhattacharya-Chatterjee
M
M
D000276:Adjuvants, Immunologic; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology* / Q000633:toxicity; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000633:toxicity; D000917:Antibody Formation; D000920:Antibody-Dependent Cell Cytotoxicity; D003110:Colonic Neoplasms / Q000276:immunology; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D008252:Macaca fascicularis; D008545:Melanoma / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D005732:Gangliosides; C019403:ganglioside, GD2; C112746:dinutuximab