CUE-101, a Novel E7-pHLA-IL2-Fc Fusion Protein, Enhances Tumor Antigen-Specific T-Cell Activation for the Treatment of HPV16-Driven Malignancies.

PURPOSE: To assess the potential for CUE-101, a novel therapeutic fusion protein, to selectively activate and expand HPV16 E711-20-specific CD8+ T cells as an off-the shelf therapy for the treatment of HPV16-driven tumors, including head and neck squamous cell carcinoma (HNSCC), cervical, and anal cancers. EXPERIMENTAL DESIGN: CUE-101 is an Fc fusion protein composed of a human leukocyte antigen (HLA) complex, an HPV16 E7 peptide epitope, reduced affinity human IL2 molecules, and an effector attenuated human IgG1 Fc domain. Human E7-specific T cells and human peripheral blood mononuclear cells (PBMC) were tested to demonstrate cellular activity and specificity of CUE-101, whereas in vivo activity of CUE-101 was assessed in HLA-A2 transgenic mice. Antitumor efficacy with a murine surrogate (mCUE-101) was tested in the TC-1 syngeneic tumor model. RESULTS: CUE-101 demonstrates selective binding, activation, and expansion of HPV16 E711-20-specific CD8+ T cells from PBMCs relative to nontarget cells. Intravenous administration of CUE-101 induced selective expansion of HPV16 E711-20-specific CD8+ T cells in HLA-A2 (AAD) transgenic mice, and anticancer efficacy and immunologic memory was demonstrated in TC-1 tumor-bearing mice treated with mCUE-101. Combination therapy with anti-PD-1 checkpoint blockade further enhanced the observed efficacy. CONCLUSIONS: Consistent with its design, CUE-101 demonstrates selective expansion of an HPV16 E711-20-specific population of cytotoxic CD8+ T cells, a favorable safety profile, and in vitro and in vivo evidence supporting its potential for clinical efficacy in an ongoing phase I trial (NCT03978689).

The Effect of Weak Confinement on the Orientation of Nanorods under Shear Flows.

We performed a numerical analysis to study the orientation distribution of a dilute suspension of thin, rigid, rod-like nanoparticles under shearing flow near a solid boundary of weak confinement. Brownian dynamics simulation of a rod was performed under various ratios of shear rate and rod diffusivity (Peclet number), as well as the center-of-mass position (wall confinement). We discuss the effects of Peclet number and wall confinement on the angle distributions, Jeffery orbit distribution and average orientation moments. The average orientation moments, obtained as a function of Peclet number and wall confinement, can be used to improve a previous shear-induced migration model. We demonstrate that the improved model can give excellent prediction of the orientation moment distributions in a microchannel flow.

Correlations between PANCE performance, physician assistant program grade point average, and selection criteria.

PURPOSE: The purpose of this study was to examine correlations between first-time Physician Assistant National Certifying Exam (PANCE) scores and pass/fail status, physician assistant (PA) program didactic grade point average (GPA), and specific selection criteria. METHODS: This retrospective study evaluated graduating classes from 2007, 2008, and 2009 at a single program (N = 119). RESULTS: There was no correlation between PANCE performance and undergraduate grade point average (GPA), science prerequisite GPA, or health care experience. There was a moderate correlation between PANCE pass/fail and where students took science prerequisites (r = 0.27, P = .003) but not with the PANCE score. PANCE scores were correlated with overall PA program GPA (r = 0.67), PA pharmacology grade (r = 0.68), and PA anatomy grade (r = 0.41) but not with PANCE pass/fail. CONCLUSIONS: Correlations between selection criteria and PANCE performance were limited, but further research regarding the influence of prerequisite institution type may be warranted and may improve admission decisions. PANCE scores and PA program GPA correlations may guide academic advising and remediation decisions for current students.