Ursula Kapp

Recent efforts to establish an in vivo model as a new experimental tool in the study of Hodgkin's disease☆

INTRODUCTION HODGKIN’S DISEASE is defined by the presence of characteristic Hodgkin (HD)-cells and Reed-Sternberg (RS)-cells surrounded by normal reactive cells including lymphocytes, benign histiocytes, plasma cells and eosinophils. The HDand RS-cells are thought to be the actual malignant cells. Despite intensive investigation the cell of origin of RS-cells has not been definitively identified. These cells only constitute 0.1-l% of the cells in involved tissues. Thus, a number of groups have attempted to establish Hodgkinand RS-cell lines. Ten tumour cell lines are currently recognised as being Hodgkin derived [l-lo] (see Table 1). Although heterogeneous, they all fulfill the criteria of monoclonality and aneuploidy. However, it is difficult to prove that these lines are true counterparts of HDand RS-cells in Go. An animal model, in which the biological conditions are more equivalent to the microenvironment of HDand RS-cells, might be advantageous for further studies of Hodgkin’s disease. Heterotransplantation of haematological malignancies has proved to be difficult [ 11, 121. Extensive immunosuppression of the athymic nude mice with treatment such as irradiation [ 131 is necessary for successful transplantation of non-Hodgkinlymphomas (NHL) and leukaemia derived cell lines. Otherwise the tumour must be injected intracranially or into the anterior chamber of the nude mouse eyes [ 11, 141. Except intracranially in vivo growth of any of the 10 available Hodgkin’s lymphoma derived cell lines or of primary biopsy specimen has not been achieved until now in nude mice [2, 151. Only one mutant subline (L540 cy, see below) transplanted subcutaneously into X linked immunodeficient/beige/nude (BNX) mice led to reproducible tumour growth and could be employed for testing the antitumour effects of ricin A-chain immunotoxins [16]. BNX mice and severe combined immunodeficient (SCID) mice appear to be better recipients for human tumours [17, 181. The BNX mouse is a cross between three murine immunodeficient strains. It is homozygous for the thymus (T cell) deficiency nude (nu)gene on chromosome 11 and the lysosomal (NK cell) defect beige gene on chromosome 13. Furthermore it carries the X chromosomal B cell regulatory gene defect. In BNX mice three specific immune defence effector cells are affected. However, there may be some remaining activity of B cells since BNX

Propagation of Hodgkin and Reed-Sternberg Cells

Tumour tissue derived from Hodgkin’s disease (HD) has been propagated in vitro and in vivo. Until now, 14 in vitro cell lines have been established, which are likely to be derived from the tumour cells of HD. These cell lines have gained importance in the diagnosis and therapy of HD by helping to define the antigens CD30, CDw70 and Ki-67, by the establishment of an animal model and by the development of new immunotherapeutic strategies.