VEGF-Trap (V-T) overcomes defects in dendritic cell (DC) differentiation without improvement in antigen-specific immune responses

21087 Background: Induction of antitumor immune responses requires adequate DC function. Well-documented DC defects in cancer mediated through tumor-derived vascular endothelial growth factor (VEGF) may lead to tumor escape and limit efficacy of cancer vaccines. V-T with extracellular domains of VEGFR 1/ 2 coupled to Fc IgG1 binds all VEGF-A isoforms. Methods: To determine if inhibition of VEGF signaling improves immune responses, we evaluated 15 cancer pts treated with V-T (2.0–7.0 mg/kg) IV over 1 hr Q 2 wks on a phase I trial. To evaluate immune parameters, PBMC were collected prior to, days 15, 29, and 57 of V-T treatment. Ligand blockade was achieved in all patients. Mature DCs (myeloid and plasmacytoid subsets), and regulatory T cells (T regs) were characterized by expression pattern of CD11c, CD86, CD40, CCR7, CD83, CD123, CD4, CD25, and GITR. T cell function was assessed by allogeneic mixed leukocyte reaction (MLR) and proliferation to tetanus toxoid, influenza, or PHA. Results: V-T treatment did ...