TUMOR-DIRECTED CYTOTOXICITY IN MULTIPLE-MYELOMA - THE BASIS FOR AN EXPERIMENTAL TREATMENT APPROACH WITH INTERLEUKIN-2

There is growing evidence that in multiple myeloma (MM) tumor-directed immune responses exist, might influence tumor progress and could be p utative targets for immunotherapeutic approaches. Peripheral blood T l ymphocytes are capable of suppressing monoclonal immunoglobulin produc tion of autologous myeloma plasma cells in vitro. This activity can be enhanced by stimulation with mitogens, OKT3 monoclonal antibody or in terleukin 2 (IL-2), and is obviously mediated by cytolytic T lymphocyt es as demonstrated in a cytotoxicity assay using purified MM plasma ce lls as targets. The lytic activity is significantly higher when the ef fecters are prestimulated with irradiated autologous MM plasma cells. Based on these results 18 MM patients of advanced stages with tumor pr ogress received 9 x 10(6) IU/m(2) recombinant IL-2 (Proleukin(R)) twic e daily on days 1 and 2 and 0.9 x 10(6) IU/m(2) twice daily for five s ubsequent days per week s.c. from days 3-56 (q 12 weeks). During thera py the number of eosinophils increased 15-fold, CD4(+) T lymphocytes w ere activated as demonstrated by CD25 antigen expression and CD56(+) n atural killer (NK) cells expanded in the peripheral blood. NK cell act ivity and lymphokine-activated killer cell activity were significantly enhanced. IL-2 therapy induced endogenous IL-2 production and elevate d soluble IL-2 receptor serum concentrations, Tumor response was obser ved in 6/17 evaluable patients. These data indicate that low-dose IL-2 treatment can stimulate immune enhancement in MM patients despite the ir characteristic tumor-induced immunodeficiency, and has proven to ha ve limited efficacy in advanced MM patients.