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Variable domains of heavy chain-only antibodies (V H H), also known as nanobodies (Nbs), are monomeric antigen-binding domains derived from the camelid heavy chain-only antibodies. Nbs are characterized by small size, high target selectivity, and marked solubility and stability, which collectively facilitate high-quality drug development. In addition, Nbs are readily expressed from various expression systems, including E. coli and yeast cells. For these reasons, Nbs have emerged as preferred antibody fragments for protein engineering, disease diagnosis, and treatment. To date, two Nb-based therapies have been approved by the U.S. Food and Drug Administration (FDA). Numerous candidates spanning a wide spectrum of diseases such as cancer, immune disorders, infectious diseases, and neurodegenerative disorders are under preclinical and clinical investigation. Here, we discuss the structural features of Nbs that allow for specific, versatile, and strong target binding. We also summarize emerging technologies for identification, structural analysis, and humanization of Nbs. Our main focus is to review recent advances in using Nbs as a modular scaffold to facilitate the engineering of multivalent polymers for cutting-edge applications. Finally, we discuss remaining challenges for Nb development and envision new opportunities in Nb-based research., Competing Interests: Declaration of Competing Interest Y.S. is a co-founder of Antenna Biotechnology Inc., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aim: This study aimed to model the financial impact of caplacizumab with therapeutic plasma exchange (TPE) + immunosuppression for patients experiencing an acute acquired thrombotic thrombocytopenic purpura (aTTP) episode versus TPE + immunosuppression, from a US hospital's perspective., Methods and Materials: We developed an economic model to estimate the impact of caplacizumab on a US hospital's budget. Cost offsets from caplacizumab utilization targeted inpatient general ward days, intensive care unit (ICU) days, and TPE utilization. Costs and event probabilities were estimated from primary data analyses of the phase 3 HERCULES trial and peer-reviewed literature or other public sources. Plan reimbursement was obtained from 2019 Medicare Fee Schedules and adjusted to represent reimbursement from different US payers. Cost of ICU and general ward utilization were estimated from Medicare Provider Analysis and Review data analyses capturing hospital discharges., Results: The model results indicate that caplacizumab leads to hospitalization cost savings of over $8,000 ($23,148 versus $14,904) along with TPE cost savings of over $14,000 ($37,150 versus $23,033) per patient. When the cost of caplacizumab and plan reimbursement are incorporated into the results, the per-patient cost of TPE + immunosuppression is $23,120 versus $70,068 for caplacizumab with TPE + immunosuppression, an incremental cost of $46,948. The model was robust to several scenario analyses; however, when limited to Medicare fee-for-service (FFS), the incremental cost of caplacizumab per patient was reduced to $4,852 due to add-on payments., Conclusions: Caplacizumab with TPE + immunosuppression is associated with an increase in costs; however, the increase is nominal among payers who provide an add-on payment consistent with that of Medicare FFS.