OBJECTIVETo investigate the antitumor immune efficiency of mouse dendritic cells (mDCs) by using adenovirus-mediated tumor necrosis factor-alpha (AdV-TNF-alpha) gene transfer.

METHODSMDCs infected with AdV-TNF-alpha and AdV-pLpA (no gene insert) at 100 multiplicity of infection (MOI) were analyzed by RNase protection assay for their cytokine secretion. Mixed lymphocyte reactions were also performed to analyze their capacity for alloantigen-presentation. C57BL/6 mice were challenged with R3LL tumor cells (Lewis lung carcinoma line) 10 days after vaccination with different engineered DCs and regular DCs as well.

RESULTSCompared to AdV-pLpA and mock-infected DCs, AdV-TNF-alpha-infected DCs displayed up-regulated expression of alpha tumor necrosis factor, interleukin-12 (IL-12), interleukin-18 (IL-18) and granulocyte macrophage colony stimulation factor (GM-CSF), and indicated stronger allogeneic T cell proliferative responses. Furthermore, vaccination of mice with dendritic cell tumor necrosis factor-alpha (DCTNF-alpha) pulsed with Mut1 peptide induced more efficient tumor-specific cytotoxic T lymphocyte (CTL) cytotoxicity against R3LL tumor cells in vitro and with efficient antitumor immunity in vivo.

CONCLUSIONThis type of engineered DCs could be applied in clinical settings of DC-based cancer vaccines.

Adenoviridae ; genetics ; Animals ; Cytokines ; biosynthesis ; Cytotoxicity, Immunologic ; Dendritic Cells ; immunology ; Gene Transfer Techniques ; Genetic Therapy ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Neoplasms, Experimental ; immunology ; therapy ; T-Lymphocytes, Cytotoxic ; immunology ; Tumor Necrosis Factor-alpha ; genetics

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.