A recombinant influenza virus with a CTLA4-specific scFv inhibits tumor growth in a mouse model.

Oncolytic viruses (OV) have shown excellent safety and efficacy in preclinical and clinical studies. Influenza A virus (IAV) is considered a promising oncolytic virus. In this report, we generated a recombinant influenza virus expressing an immune checkpoint blockade agent targeting CTLA4. Using reverse genetics, a recombinant influenza virus, termed rFlu-CTLA4, encoding the heavy chain of a CTLA4 antibody on the PB1 segment and the light chain of the CTLA4 antibody on the PA segment was produced. RFlu-CTLA4 could replicate to high titers, and antibodies were produced in the allantoic fluid of infected eggs. Furthermore, the selective cytotoxicity of the virus was higher in various hepatocellular carcinoma cancer cell lines than in the normal cell line L02 in vitro, as indicated by MTS assays. More importantly, in a subcutaneous H22 mouse hepatocarcinoma model, intratumoral injections of rFlu-CTLA4 inhibited the growth of treated tumors and increased the overall survival of mice compared with injections of the PR8 virus. Taken together, these results warrant further exploration of this novel recombinant influenza virus for its potential use as a single or combination agent for cancer immunotherapy.

[The study on the value of using the chronic obstructive pulmonary disease and asthma physiology score to assess the severity of acute exacerbation in patients with chronic obstructive pulmonary disease complicated by type II respiratory failure].

OBJECTIVE: To explore the value of the chronic obstructive pulmonary disease (COPD) and asthma physiology score (CAPS) in evaluating the severity and prognosis of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated by type II respiratory failure. METHODS: Eighty-two cases with AECOPD complicated by type II respiratory failure between January 2005 and March 2009 were retrospectively analyzed. The severity in survivors and non-survivors was evaluated by CAPS and acute physiology and chronic health evaluation system (APACHE II score, APACHE III score), and retrospective and statistical analyses of all data were performed. RESULTS: CAPS, APACHE II score, APACHE III score, duration of invasive positive pressure ventilation (IPPV) and days in intensive care unit of 19 cases in the death group were 34.21+/-9.89, 22.53+/-7.49, 75.11+/-18.07, (25.06+/-24.64) days, (32.42+/-25.49) days , respectively, while 63 cases of the survival group were 27.41+/-8.15, 18.65+/-5.34, 64.11+/-15.92, (5.23+/-5.50) days, (12.51+/-20.70) days, respectively, and there were significant differences between two groups (P<0.05 or P<0.01). The areas under receiver operating characteristic (ROC) curves of CAPS, APACHE II score and APACHE III score were 0.712 (P=0.005), 0.654 (P=0.043) and 0.655 (P=0.042), respectively. When CAPS score was 30.5, Youden index was the highest (0.435). The mortality rate had a positive correlation with CAPS. When the CAPS score was over 30, there was a tendency of increase in mortality rate. CONCLUSION: CAPS is very useful to evaluate the severity and prognosis of patients with AECOPD complicated by type II respiratory failure. It is easy to perform, and better than APACHE II and APACHE III.