A mouse model for the Sézary syndrome

Immune deficient CB-17 SCID beige mice were injected subcutaneously with HUT78 cells, a cell line, derived from a Sézary syndrome patient. Developing tumors were analyzed by immunohistochemistry.Injected HUT78 cells formed tumors at the site of injection. In contrast to the Sézary syndrome in man, no malignant cells were observed in the blood of tumor bearing CB-17 SCID beige mice. The tumors appeared 44-62 days after injection and tumor bearing mice survived further 25 - 62 days until they had to be euthanized according to the guidelines of the Swiss animal protection law, since the tumors had reached the maximal allowed size.Although the mouse model does not exactly match the human disease, it will be suited for tests of new substances for the treatment of the Sézary syndrome. The formation of an isolated tumor on the skin has the advantage that the effect of a potential drug can be directly monitored without the use of invasive methods.Cutaneous T cell lymphomas (CTCL) are a class of non-Hodgkin's lymphomas characterized by clonal proliferation of neoplastic T-lymphocytes [1-3]. The two main forms are Mycosis fungoides (MF) and its leukemic counterpart, the Sézary syndrome (SzS). MF remains confined to the skin and often presents with patches and plaques or in more advanced forms with tumors and a generalized erythema (erythroderma). Sometimes MF proceeds to SzS. Sézary Syndrome patients show generalized erythroderma, leukemic T cells in the blood and a reduced life expectancy compared to MF patients with only approximately 30% of patients surviving beyond 5 years after diagnosis. This is probably due to the circulating malignant T cells producing various immunosuppressant molecules such as IL-10, which can lead to down regulation of the immunological tumor surveillance.Sézary syndrome patients are treated with psoralen and UVA (PUVA) in combination with interferon alpha, locally applied cytostatic substances such as BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea), o