Immunostimulatory Activity of Dendritic cells pulsed with carbonic anhydrase IX and Acinetobacter baumannii outer membrane protein A

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.

Generation of anti-tumour immune response using dendritic cells pulsed with carbonic anhydrase IX-Acinetobacter baumanniiouter membrane protein A fusion proteins against renal cell carcinoma

“…Follow-up experiments using AbOmpA found that DCs pulsed with AbOmpA alone or in combination with autologous tumour cell lysates suppressed tumour growth in mice with a murine B16 melanoma [27]. More recently, we examined the immunostimulatory activity of DCs pulsed with a combination of CA9 and AbOmpA in vitro in order to determine the potential of AbOmpA in DC-based immunotherapy against RCC [37]. Use of a combination of CA9 and AbOmpA proteins resulted in more efficient induction of DC maturation and T cell response than CA9 alone, suggesting a potential of AbOmpA for enhancement of anti-tumour immune response against RCC.…”

Host Innate Immune Responses to Acinetobacter baumannii Infection

“…The ability of OmpA to activate DCs was further supported by the observation that OmpA might function as an adjuvant in DC-based cancer immunotherapy (Kim et al, 2011(Kim et al, , 2012, in that OmpA-pulsed DCs significantly enhanced the number of IL-2 producing CD8 + T cells and IFN-γ producing CD4 + T cells, inhibited the tumor growth, and improved the survival of tumor-bearing mice (Lee et al, 2008;Kim et al, 2012). Although most studies showed that the immune responses induced by A. baumannii-activated DCs were primarily Th1 biased (Debarry et al, 2007(Debarry et al, , 2010, recent studies showed that OMVs from an A. baumannii clinical strain activated BMDCs to promote Th2 responses (Cai et al, 2019).…”

Carbonic Anhydrase IX in Renal Cell Carcinoma, Implications for Disease Management

“…The main one was the use of dendritic cells (DCs, specific tumor antigen presentation) via an introduction of a granulocyte-macrophage colony stimulating factor (GMCSF)-CAIX fusion protein (produced by viral bioengineering), in order to activate DCs and thus trigger a CD8+ mediated, CAIX targeted, antitumoral response. Kim et al [ 50 ] presented the results of a pre-clinical study in 2011 aiming to activate DCs by a combination of CAIX and Acinetobacter baumannii outer membrane protein A (AbOmpA) in a murine model [ 51 ]. A significant immunostimulatory of DCs was observed via secretion of IL-2 and interferon (IFN)γ in T-cells.…”