We found that three tumor patients treated with mouse mAbs have T cells that recognize processed mouse Ig on autologous APC in a class II-restricted fashion, and we have shown that mouse mAbs directed against various cell surface molecules can be used as antigens to focus these T cells on an MHC class II-positive target of choice.

AbstradThe 52 kD myeloid membrane glycoprotein CDI 4 represents the receptor for complexes of lipopolysaccharide (LPS) and LPS binding protein (LBP); it is involved in LPS induced tumor necrosis factor-alpha production. Expression of CD14 increases in monocytes differentiating into macrophages, and it is reduced by rlFNg in monocytes in vitro. In the present study CD14 membrane antigen expression was investigated in cultures of human mononuclear leucocytes (PBL), in elutriated, purified monocytes, and in blood monocyte derived Teflon cultured macrophages. Cells were incubated for 15 or 45 h with rlL-I, rlL-2, rlL-3, rIL-4, rlL-5, rlL-6, rTNFa, rGM-CSF, rM-CSF, rTGFbl, rlFNa, lipopolysaccharide (LPS), and, as a control, rlFNg. The monoclonal antibodies Leu-M3 and MEM 18 were used for labelling of CD14 antigen by indirect immunofluorescence and FACS analysis of scatter gated monocytes or macrophages. lFNg concentrations were determined in PBL culture supernatants by ELISA. rlFNa and rlL-2 reduced CDI 4 in 15 and 45 h PBL cultures, an effect mediated by endogenous IFNg, since it was abolished by simultaneous addition of an anti-IFNg antibody. rlFNa and rlL-2 were ineffective in purified monocytes or macrophages. rlL-4 strongly reduced CDI 4 in PBL and purified monocytes after 45 h, whereas in macrophages the decrease was weak, although measurable after 15 h. The other cytokines investigated did not change CD14 antigen expression. Cycloheximide alone reduced CDI 4, but when added in combination with rlFNg the effect on CD14 downregulation was more pronounced. The effect of rlFNg on CD14 in PBL cultures was dose-dependently inhibited by rlL-4 and this inhibition is probably due to an IL-4 mediated blockade of lFNg secretion. LPS at a low dose increased CD14, at a high dose it produced a variable decrease of CD14 in PBL, which was probably due to LPS induced lFNg secretion. LPS strongly enhanced CDI 4 in 45 h cultures of purified monocytes. The results, showing that CD14 antigen expression is upregulated by LPS and downregulated by rlFNg and rlL-4, suggest that the LPS-LBP receptor is involved in the feedback response of IFNg and IL-4 to LPS stimulation.

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The results indicate that ondansetron given orally for 15 days is safe and effective in the control of emesis induced by CMF. It is however too early to recommend ondansetron as standard antiemetic therapy for oral CMF, as the treatment of nausea and vomiting in this setting has not been studied thoroughly enough.