The long-term objective of this research plan is the effective use of interferon as a new modality in the treatment of lymphoma. Alpha 2 interferon, prepared by recombinant DNA technique, will be given as an adjuvant to patients with advanced stage, low-grade subtypes of non-Hodgkin's lymphoma who have achieved complete remission with cytoxan, vincristine and prednisone chemotherapy. This will be a controlled, randomized trial in which interferon is given in four separate courses on a daily basis using an antiproliferative dose. Patients receiving interferon will be monitored for safety and immunologic functions, including lymphocyte subset analysis, Beta2 microglubulin and Fc-Gamma receptor expression, monocyte activation and natural killer cell activity. This clinical trial will test the ability of interferon to extend the duration of complete remission and assess the toxicity of its use as an adjuvant after chemotherapy. Retrospective correlation of the immunologic and clinical effects will become possible as the study matures. Interferon will also be studied in combination with another new treatment modality, monoclonal antibodies, to determine the ability of interferon to augment or potentiate antibody-mediated cytotoxicity. Animal studies using a monoclonal antibody to the idiotype of a murine lymphoma will be conducted to determine the optimal clinical and immunologic effects of the interferon-monoclonal antibody combination. In vitro studies are designed to assess the ability of different species of interferon to enhance possible effector cell systems involved in the cytotoxicity mediated by monoclonal antibodies. Killer cells, monocyte-macrophages and polymorphonuclear cells will be analyzed with and without interferon in an antibody-dependent cellular cytotoxicity assay using B and T cell lines and monoclonal antibodies of various specificity and isotype. Clinical studies using combination therapy with interferon and monoclonal antibodies are planned in selected lymphoma patients based on the results in our animal model and in vitro system. These studies will explore and develop the use of combination thereapy with an increasing number of clinically available interferons and monoclonal antibodies. The ability of interferon to serve as a toleragen for mouse immunoglobulin will also be explored in our clinical studies. In sum, this research plan integrates clinical and laboratory activities designed to optimize the clinical effects and further characterize the immunologic effects of interferon in human lymphoma.
| Basham, T Y; Kaminski, M S; Kitamura, K et al. (1986) Synergistic antitumor effect of interferon and anti-idiotype monoclonal antibody in murine lymphoma. J Immunol 137:3019-24 |
