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Enhancement of anti-murine colon cancer immunity by fusion of a SARS fragment to a low-immunogenic carcinoembryonic antigen

DOI: 10.1186/1480-9222-14-2

Keywords: immunotherapy, tumor-derived peptide, tumor vaccine, low-immunogenicity

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Abstract:

To enhance the immune efficiency of CEA in mice that received, we fused a partial CEA gene with exogenous SARS-CoV fragments. Oral vaccination of an attenuated Salmonella typhimurium strain transformed with plasmids encoding CEA-SARS-CoV fusion gene into BALB/c mice elicited significant increases in TNF-α and IL-10 in the serum. In addition, a smaller tumor volume was observed in CT26/CEA-bearing mice who received CEA-SARS-CoV gene therapy in comparison with those administered CEA alone.The administration of fusing CEA-SARS-CoV fragments may provide a promising strategy for strengthening the anti-tumor efficacy against low-immunogenic endogenous tumor antigens.Tumor-associated antigens (TAAs) are attractive candidates for cancer therapy in view of their specificity to tumor targets and safety profile. Although most known tumor antigens can generate cancer-specific immune responses, they are either poorly immunogenic or functionally non-immunogenic, and may not elicit immune responses sufficient to eradicate tumor cells [1]. Therefore, efforts to enhance TAA-mediated host immunity towards tumors are being made by exploring a variety of adjuvants for immunotherapy, adjuvants for cancer vaccines such as highly-immunogenic vectors, combinations of T-cell co-stimulatory molecules, or immune-stimulatory cytokines usually being employed [2]. Carcinoembryonic antigen (CEA) is a well-known and over-expressed TAA in most human colon carcinomas, and vaccination with CEA has been demonstrated to induce, although with only minor effects, both humoral and T-cell responses [3]. In order to magnify the CEA-mediated tumor-specific immune activities, co-administration of CEA with other immune-response enhancers such as granulocyte-macrophage colony-stimulating factor (GM-CSF) [4] or interleukin (IL)-12 [5] has yielded promising results with regards to the activation of cellular and humoral CEA-specific immune responses.Some antigenic peptides derived from the severe acute respiratory

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