127 Tenfold Reduction of the Therapeutic Dose of Tumor Necrosis Factor Through Combination with Alpha-galactosylceramide

Abstract

was approved by the University of North Carolina Institutional Review Board and all patients provided written informed consent prior to enrollment. Results: iC3b baseline conc was elevated in one patient that had an infusion reaction compared to non-reactors (82.9 vs. 21.5±11.6 ng/ml). Higher complement was associated with higher CL (R=0.74, P=0.001). There was an inverse relationship between iC3b baseline conc and the maximum grade of PPE (r = −0.90, P=0.0004). The chemokine AUC score was positively associated with encapsulated dox AUC Z-score (R=0.79, P=0.0006). There was a positive linear relationship between the CCL2 AUC and % decrease in MO (r=0.66, P=0.037). Conclusions: These findings suggest that complement and chemokine mediators of the MPS are associated with PLD PK and PD. Complement levels may be useful to predict CL and toxicity of PLD. These results also suggest that PLD may have a positive feedback effect on the MPS via the stimulation of chemokine production. Further studies are warranted to elucidate mechanisms underlying interaction between immune mediators and MPS and PLD and to individualize therapy with PLD and future NPs in the treatment of EOC and other diseases.