Intratumoral Injection of Large Surface Area Microparticle Taxanes in Carcinomas Increases Immune Effector Cell Concentrations, Checkpoint Expression, and Synergy with Checkpoint Inhibitors: A Review of Preclinical and Clinical Studies.

This review summarizes development of large surface area microparticle paclitaxel (LSAM-PTX) and docetaxel (LSAM-DTX) for local treatment of primary carcinomas with emphasis on immunomodulation. Intratumoral (IT) delivery of LSAM-PTX and LSAM-DTX provides continuous, therapeutic drug levels for several weeks. Preclinical studies and clinical trials reported a reduction in tumor volume (TV) and immunomodulation in primary tumor and peripheral blood with increases in innate and adaptive immune cells and decreases in suppressor cells. Increased levels of checkpoint expression of immune cells occurred in clinical trials of high-risk non-muscle-invasive bladder cancer (LSAM-DTX) and unresectable localized pancreatic cancer (LSAM-PTX). TV reduction and increases in immune effector cells occurred following IT LSAM-DTX and IT LSAM-PTX together with anti-mCTLA-4 and anti-mPD-1, respectively. Synergistic benefits from combinatorial therapy in a 4T1-Luc breast cancer model included reduction of metastasis with IT LSAM-DTX + anti-mCTLA-4. IT LSAM-PTX and LSAM-DTX are tumoricidal, immune enhancing, and may improve solid tumor response to immune checkpoint inhibitors without additional systemic toxicity.

Effect of visual cues on the resolution of perceptual ambiguity in Parkinson's disease and normal aging.

Parkinson's disease (PD) and normal aging have been associated with changes in visual perception, including reliance on external cues to guide behavior. This raises the question of the extent to which these groups use visual cues when disambiguating information. Twenty-seven individuals with PD, 23 normal control adults (NC), and 20 younger adults (YA) were presented a Necker cube in which one face was highlighted by thickening the lines defining the face. The hypothesis was that the visual cues would help PD and NC to exert better control over bistable perception. There were three conditions, including passive viewing and two volitional-control conditions (hold one percept in front; and switch: speed up the alternation between the two). In the Hold condition, the cue was either consistent or inconsistent with task instructions. Mean dominance durations (time spent on each percept) under passive viewing were comparable in PD and NC, and shorter in YA. PD and YA increased dominance durations in the Hold cue-consistent condition relative to NC, meaning that appropriate cues helped PD but not NC hold one perceptual interpretation. By contrast, in the Switch condition, NC and YA decreased dominance durations relative to PD, meaning that the use of cues helped NC but not PD in expediting the switch between percepts. Provision of low-level cues has effects on volitional control in PD that are different from in normal aging, and only under task-specific conditions does the use of such cues facilitate the resolution of perceptual ambiguity.