Mature dendritic cells induce T-helper type-1-dominant immune responses inpatients with metastatic renal cell carcinoma

We performed a pilot study on a dendritic cell (DC)-based vaccine in 4 pati ents with advanced renal cell carcinoma. The vaccine consisted of cultured blood DCs loaded with autologous tumor cell lysate plus keyhole limpet hemo cyanin (KLH) and matured with a combination of tumor necrosis factor alpha and prostaglandin E-2 We describe the immune response against KLH induced b y DC-based immunization in a patient undergoing an objective partial respon se and compare it with the responses observed in patients with either stabl e or progressive disease. The patient with the clinical response developed strong delayed-type hypersensitivity (DTH) against KLH after a single vacci nation with antigen-loaded DCs, whereas the other patients failed to develo p DTH reactivity even after repeated vaccinations. Antigenic stimulation of mononuclear cells (MNCs) induced proliferation and IFN-gamma but not IL-4 production as well as expression of the chemokine receptor CXCR3 consistent with a T-helper (Th) type-1 bias. Exogenous IL-12 enhanced and exogenous I L-4 diminished IFN-gamma production. In the 2 patients with stable disease two or more vaccinations were required to induce maximal MNC responses. In the patient with progressive disease MNC responses were hardly detectable. Anti-KLH antibodies appeared with different kinetics but could be detected in the serum of all patients. Isotype analysis revealed the presence of IgM , IgG(1), IgG(2) and IgG(3) as well as IgA and complete absence of IgE. The patient with progressive disease also developed IgG(4) antibodies indicati ve of a deviation towards Th2. Cultured blood DCs can be a potent vaccine f or the antigen-specific immunization of patients with advanced kidney cance r. KLH serves as a tracer molecule which allows determination of the magnit ude, kinetics and Th bias of the cellular and humoral immune response induc ed by DC-based immunization. The data also suggest that Th type-1-dominant immune responses involving DTH reaction are required for the induction of t umor regression. Copyright (C) 2000 S. Karger AG, Basel.