IDIOTYPE VACCINES FOR NON-HODGKINS-LYMPHOMA INDUCE POLYCLONAL IMMUNE-RESPONSES THAT COVER MUTATED TUMOR IDIOTYPES - COMPARISON OF DIFFERENTVACCINE FORMULATIONS

The idiotype (Id) of the Ig expressed on the surface of non-Hodgkin's lymphoma cells is a suitable target for immunotherapy. Indeed, treatme nt with monoclonal anti-id antibodies (Abs) can induce long-lasting cl inical remissions. However, some of the treated patients relapse with a tumor expressing lg with point mutations in the idiotope recognized by the particular monoclonal antibody (MoAb). The alternative approach of active immunization with tumor Id can cure the disease in mice wit h established tumors and is now being studied in clinical trials, Here , we tested the hypothesis that active immunization with the idiotype would evoke a polyclonal immune response that would cover mutated tumo r variants. As a test system, we chose the tumor from a patient who ha d achieved a complete remission after therapy with anti-id Ab but subs equently relapsed with a mutated tumor variant no longer binding the t reatment Ab. Mice were immunized with proteins and genetic vaccines de rived from the original tumor, including (1) Id-keyhole limpet hemocya nin protein, (2) Id single-chain variable fragment (scFv) granulocyte- macrophage colony-stimulating factor (GM-CSF) protein, (3) DNA encodin g the Id, and (4) an adenovirus encoding the Id. All immunized mice de veloped a specific immune response detecting tumor-derived Id proteins from the original tumor and from all tumor variants, We conclude that active immunization with tumor Id can induce a polyclonal immune resp onse and therefore may prevent the escape of mutated tumor variants. ( C) 1997 by The American Society of Hematology.