A novel strategy for immunotherapy using antibody-coupled carriers to focus cytotoxic T helper cells.

Targeting of cytotoxic T cells to cell-bound antigens has previously been reported using bispecific antibodies. In this report we document a novel targeting system whereby cytotoxic T helper (Thc) cells were targeted to a B cell lymphoma by means of an anti-idiotypic antibody (anti-Id), specific for the surface immunoglobulin of the B cell, coupled to the carrier protein keyhole limpet hemocyanin (KLH). In this system the anti-Id-KLH complex bound to the Id determinant of the surface immunoglobulin of the B cell lymphoma. This complex was then presented in a major histocompatibility complex class II-restricted manner to the KLH-specific Thc cell (KLH55) which was induced into its cytolytic pathway through the specific recognition of KLH. The uniqueness of this system was that it utilized the inherent ability of the target B cell to process and present antigen. This offered the distinct advantage that processed antigen re-expressed on the cell membrane was in a more stable form, thereby enabling the target cell to remain susceptible to cytotoxicity for an extended period of time. Furthermore, as is characteristic of Thc cells in general, bystander killing was demonstrated and Id (or Ia)-negative mutants of the target cell did not escape destruction. The adaptation of such a system will have useful implication for future immunotherapeutic strategies.