Abstract:Major advances in therapeutic proteins, including antibody-drug conjugates (ADCs), have created revolutionary drug delivery systems in cancer over the past decade. While these immunoconjugate agents provide several advantages compared to their small-molecule counterparts, their clinical use is still in its infancy. The considerations in their development and clinical use are complex, and consist of multiple components and variables that can affect the pharmacologic characteristics. It is critical to understand the mechanisms employed by ADCs in navigating biological barriers and how these factors affect their biodistribution, delivery to tumors, efficacy, and toxicity. Thus, future studies are warranted to better understand the complex pharmacology and interaction between ADC carriers and biological systems, such as the mononuclear phagocyte system (MPS) and tumor microenvironment. This review provides an overview of factors that affect the pharmacologic profiles of ADC therapies that are currently in clinical use and development.
Objective. The purpose of this review is to discuss some principles from cognitive psychology regarding the benefits of testing and translate those findings into practical applications for instruction and studying. Findings. Testing or retrieval practice is superior to re-study for promoting long-term retention. The benefits of testing can be see with open-ended responses (eg, cued or free recall) and multiple choice questions. The use of multiple-choice questions during testing may have an additional benefit as it may stabilize information that is stored in memory but temporarily inaccessible due to disuse (eg, marginal knowledge). Summary. Testing can have multiple learning benefits. We emphasize that incorporating opportunities for retrieval after teaching is an essential component of lasting learning. In addition, retrieval practice can be incorporated in all aspects of instruction.
CYP3A5 genotype is the most significant genetic factor that impacts tacrolimus dose among the genes studied. This study generated the first pharmacogenomics model that predicts tacrolimus stable dose based on age, ethnicity, genotype and comedication use. Our results highlight the importance of incorporating both genetic and clinical, demographic factors into dose prediction.
The rapid advancement in the development of therapeutic proteins, including monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs), has created a novel mechanism to selectively deliver highly potent cytotoxic agents in the treatment of cancer. These agents provide numerous benefits compared to traditional small molecule drugs, though their clinical use still requires optimization. The pharmacology of mAbs/ADCs is complex and because ADCs are comprised of multiple components, individual agent characteristics and patient variables can affect their disposition. To further improve the clinical use and rational development of these agents, it is imperative to comprehend the complex mechanisms employed by antibody-based agents in traversing numerous biological barriers and how agent/patient factors affect tumor delivery, toxicities, efficacy, and ultimately, biodistribution. This review provides an updated summary of factors known to affect the disposition of mAbs/ADCs in development and in clinical use, as well as how these factors should be considered in the selection and design of preclinical studies of ADC agents in development.
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