Abstract

Dendritic cell (DC)-based immunotherapy is a potent therapeutic modality for treating renal cell carcinoma (RCC), but development of antigens specific for tumor-targeting and anti-tumor immunity is of great interest for clinical trials. The present study investigated the ability of DCs pulsed with a combination of carbonic anhydrase IX (CA9) as an RCC-specific biomarker and Acinetobacter baumannii outer membrane protein A (AbOmpA) as an immunoadjuvant to induce anti-tumor immunity against murine renal cell carcinoma (RENCA) in a murine model. Murine bone-marrow-derived DCs pulsed with a combination of RENCA lysates and AbOmpA were tested for their capacity to induce DC maturation and T cell responses in vitro. A combination of RENCA lysates and AbOmpA up-regulated the surface expression of co-stimulatory molecules, CD80 and CD86, and the antigen presenting molecules, major histocompatibility (MHC) class I and class II, in DCs. A combination of RENCA lysates and AbOmpA also induced interleukin-12 (IL-12) production in DCs. Next, the immunostimulatory activity of DCs pulsed with a combination of CA9 and AbOmpA was determined. A combination of CA9 and AbOmpA up-regulated the surface expression of co-stimulatory molecules and antigen presenting molecules in DCs. DCs pulsed with a combination of CA9 and AbOmpA effectively secreted IL-12 but not IL-10. These cells interacted with T cells and formed clusters. DCs pulsed with CA9 and AbOmpA elicited the secretion of interferon-γ and IL-2 in T cells. In conclusion, a combination of CA9 and AbOmpA enhanced the immunostimulatory activity of DCs, which may effectively induce anti-tumor immunity against human RCC.

• Keywords: renal cell carcinoma;dendritic cells;outer membrane protein A;carbonic anhydrase IX