Overcoming the On-Target Toxicity in Antibody-Mediated Therapies via an Indirect Active Targeting Strategy.

Antibody-based therapies could be led astray when target receptors are expressed on nontarget sites, and the on-target toxicity poses critical challenges to clinical applications. Here, a biomimetic indirect active targeting (INTACT) strategy is proposed based on receptor expression disparities between nontarget sites and the targets. By prebinding the antibodies using cell membrane vesicles with appropriate receptor expressions, the INTACT strategy could filter out the interactions on nontarget sites due to their inferior receptor expression, whereas ensure on-demand release at the targets by competitive binding. The strategy is verified on CD47 antibody, realizing drastic alleviation of its clinically concerned hematotoxicity on a series of animal models including humanized patient-derived xenograft platforms, accompanied by preferable therapeutic effects. Furthermore, the INTACT strategy proves extensive applicability for various systems including antibody, antibody-drug conjugate, and targeted delivery systems, providing a potential platform refining the specificity for frontier antibody-related therapies.

Be in Your Element: The Joint Effect of Human Resource Management Strength and Proactive Personality on Employee Creativity.

Employee creativity is fast becoming a part and parcel in the wake of the increasing volatility of the employment market and the complexity of job demands. Drawing from the actor-context interactionist theoretical approach and career construction theory, this paper adds to current research by exploring the serial mediating effect of job crafting (JC) and career adaptability (CA) in the impact of human resource management strength (HRMS) on employee creativity. Furthermore, we suggest that proactive personality interacts with HRMS to jointly influence creativity. Survey data from samples of 297 (Study 1) and 390 (Study 2) employees largely confirm our model. Our findings show that HRMS positively impacts employee creativity via serial mediation of job crafting and career adaptability, and proactive personality negatively moderates the process. The paper confirms and expands the interactionist theoretical perspective of creativity, highlights the significance of integration of contextual factors, individual characteristics, and career construction, and makes certain practical sense.