A Murine T-Cell Lymphoma Model Showing Protection Against Tumor Development and Treatment of Established Disease

Abstract

Patients suffering from leukemic and erythrodermic cutaneous T-cell lymphoma (CTCL) treated with photopheresis demonstrate a profound and prolonged clinical response that appears to be mediated immunologically. Photopheresis involves exposure of the peripheral blood lymphocytes from a patient to 8-methoxypsoralen (8-MOP) photoactivated with ultraviolet A light (UVA), with subsequent reinfusion of the treated cells.

We have evaluated the capacity of mice pretreated with chemically or photochemically altered tumor cells to induce protection against tumor development in a murine lymphoma model using a T-cell hybridoma. When injected subcutaneously into genetically compatible hybrid mice, a T-cell hybridoma leads to the development of a rapidly progressive lymphoma that metastasizes to internal organs, causing death of all the mice within four to six weeks. For the induction of protection against this murine T-cell lymphoma, mice were immunized with altered tumorogenic cells. Our data indicate that the most effective method to induce protection against tumor development in 66% of treated mice involved predamaging tumor cells with 8-methoxypsoralen photoactivated with ultraviolet A light. We have demonstrated that this protection is T-cell mediated by treating nude mice in a similar fashion without inducing protection against tumor development. We have demonstrated that there is cross-protection to another T-cell hybridoma differing in T-cell receptor specificity and to the parental thymoma. We have also demonstrated successful treatment of 64% of mice with established disease. Adoptive transfer experiments have demonstrated that this protection against tumor development is transferable by spleen cells from immune-protected mice. Adoptive transfer experiments with specific-cell-subtype depletion and isolation of immunogenic peptides will help to clarify the conditions most conducive to an anti-T-cell tumor response, and to identify its target molecules and the cells involved.