Effects of immunotherapy on experimental immunodeficiency-related lymphoproliferative disease

Background. Human lymphokine-activated cells (LAK cells) and interferon alpha (IFN-α) have been used clinically in the therapy of posttransplant lymphoproliferative disease (PTLD). However, the efficacy of such therapy has not been extensively tested under controlled experimental conditions. Methods. A B-cell line, derived from PTLD tissue and clonally related to the parent lesion, was tested for its response to IFN-α in vitro. The effects of LAK cells and IFN-α therapy were examined in a severe combined immunodeficiency disease (SCID) mouse model in vivo. Results. The PTLD cell line studied showed a 30% decrease in the rate of growth upon incubation with 500 U/ml of IFN-α. This in vitro response was also reproduced in vivo, in tumor therapy studies conducted in SCID mice. The magnitude of this inhibitory effect in vivo was a function of tumor burden and dose of IFN-α. In parallel experiments, LAK cells reduced the tumorigenicity of a lymphoblastoid cell line derived from the peripheral blood of a patient with PTLD, and prolonged the survival of SCID-beige mice with established lymphoproliferative disease. In contrast with two prior studies, in which the use of autologous cytotoxic T cells was found to be necessary, we found the administration of third-party non-HLA-matched LAK cells also to be effective in reducing tumor burden. Conclusions. These observations demonstrate the efficacy of immunotherapy for lymphoproliferative disease under controlled experimental conditions, and validate currently ongoing efforts exploring the utility of such therapy in the clinical setting.