One strategy in cancer immunotherapy is to capitalize on the key immunoregulatory and antigen presenting capabilities of dendritic cells (DCs). This approach is dependent on efficient delivery of tumor specific antigens to DCs, which subsequently induce an anti-tumor T-cell mediated immune response. Human adenovirus serotype 5 (HAdV5) has been used in human studies for gene delivery, but has limited infection in DCs, which lack the proper receptors. Addition of the porcine fiber knob (PK) from porcine adenovirus type 4 to HAdV5 allows the virus to deliver genetic material via binding to glycosylated surface proteins and bypasses the coxsackie-and-adenovirus receptor required by wild-type HAdV5. In this study we explored the potential therapeutic applications of an adenovirus with PK-based tropism against cancers expressing mesothelin. Infectivity and gene transfer assays were used to compare Ad5-PK to wild-type HAdV5. Mouse models were used to demonstrate peptide specificity and T-cell responses. We show that the PK modification highly augmented infection of DCs, including the CD141+ DC subset, a key subset for activation of naïve CD8+ T-cells. We also show that Ad5-PK increases DC infectivity and tumor specific antigen expression. Finally, vaccination of mice with the Ad5-PK vector resulted in enhanced T-cell-mediated interferon gamma (IFN-γ) release in response to both mesothelin peptide and a tumor line expressing mesothelin. Ad5-PK is a promising tool for cancer immunotherapy as it improves infectivity, gene transfer, protein expression, and subsequent T-cell activation in DCs compared to wild-type HAdV5 viruses.

Objectives: The prophylactic treatment of uncomplicated TBAD with TEVAR is controversial. This warrants the identification of a high-risk category of dissections that may particularly benefit from surgical intervention. The analysis of radiographic features presents a promising modality of assessing this high-risk cohort. We test the ability of aortic size and shape metrics from the literature to predict patient suitability for TEVAR from pre-operative imaging. Methods: We collected a single institutional retrospective cohort of 36 patients with TBAD who received TEVAR and had pre-operative and follow-up CTA imaging. We tested 8 aortic size and shape metrics. We segmented each patient’s aorta and true lumen from the pre-operative scan. Tortuosity, mean diameter, centerline curvature, and eccentricity were measured from the centerline. True and false lumen volumes and max diameter were calculated. The question mark angle, as previously defined by Li et al., was also measured. Univariate and multivariate logistic regression analyses were performed. Results: In the univariate analysis, pre-operative false lumen volume (OR 26.2 95% CI 2.72 to 252, p = .005), mean diameter (OR 9.6 95% CI 2.19 to 42.3, p = .003), and maximum diameter (OR 9.0 95% CI 2.12 to 38.3, p = .003) were all significantly associated with post-TEVAR outcomes. Tortuosity index (OR 2.7, 95% CI 1.14 to 6.37, p = .024) was the only significant shape parameter. In multivariate analysis, we found that pre-operative maximum diameter (OR 10.0, 95% CI 1.50 to 67.0, p < .018) is a significant predictor of TEVAR outcomes independent of shape parameters, all of which were not significant. Conclusions: False lumen volume and maximum diameter can predict the occurrence of reintervention and type I endoleak following TEVAR for uncomplicated TBAD. While size measures are effective in explaining aortic dissection behavior, current shape measures are not as effective and better methodologies must be developed.