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Generation of monoclonal antibodies utilizing the host anti-idiotypic network.

In accordance with Jerne's idiotypic network theory, it was attempted to generate antibodies utilizing the host's anti-idiotypic reactions. A murine anti-tumour monoclonal antibody was administered to rats; we examined the possibility of whether the animals would develop anti-idiotypic antibodies, the paratope of which would be the "internal image" of the tumour associated antigen that the original murine monoclonal antibody recognizes. These anti-idiotypic antibodies would generate a second generation of anti-idiotypic antibodies, which would have the same specificity as the immunogen murine antibody. It was found that, while all rats had no anti-tumour response prior to immunization with the anti-tumour murine monoclonal antibody, they all developed antitumour antibodies following administration. The latter observation came as a consequence of the development of anti-mouse immunoglobulin and anti-idiotypic antibodies. The animals were sacrificed and their spleen cells were fused with myeloma cells for the production of monoclonal rat anti-tumour antibodies. Finally, a monoclonal antibody was selected which appeared to recognize the same tumour-associated antigen as the originally administered murine antibody, as shown by cell-binding and competition assays, as well as immunohistochemistry. This new approach allows for "replication" of polyclonal and monoclonal antibodies without the need of the antigen and it may also serve as an immunotherapy strategy for the augmentation of the antitumour immune response of patients receiving monoclonal antibody treatment.