Clinical studies with anti-idiotypic monoclonal antibody BEC2 that mimics GD3 ganglioside

Abstract

Anti-idiotype (anti-Id) monoclonal antibodies (mAb) as antitumor vaccines offer several potential advantages over vaccines constructed from the actual antigen. One of the advantages relates to anti-Id mAb that mimic nonprotein antigens. Classically, nonprotein antigens are not recognized by T cells and the antibody responses against these antigens consist largely of low-affinity IgM antibodies (a T-cell-independent response). Anti-Id mAb are immunoglobulin proteins that can express T-cell epitopes necessary for helper T-cell responses. As a result, immune responses induced by anti-Id mAb may be T-cell dependent and induce high affinity IgG antibodies against the original antigen. The study presented in this chapter illustrates this potential advantage of anti-Id mAb vaccines by producing an anti-Id mAb that mimics GD3 ganglioside with the goal of using the anti-Id mAb to induce antibody responses against GD3. GD3 ganglioside is a melanoma tumor antigen that is poorly immunogenic. To produce an anti-Id mAb that mimics GD3, syngeneic mice were immunized with R24 mAb and hybridomas were produced and cloned. Two anti-Id mAb were isolated, designated BEC2 and BEC3, and were shown to have slightly different specificities. When used to immunize rabbits, only BEC2 induced antibodies against GD3, and so BEC2 was used in all further studies.