SCAFFOLD PROTEIN FREE
10 Moreover, it may be difficult to introduce free residues and chemical linkers for further drug conjugation. 9 Posttranslational modifications are indispensable in facilitating the production of antibodies with complete functionality however, these require the use of a high-cost and time-consuming eukaryotic expression system, which limits the large-scale production and access to most patients. For instance, the large molecular weight leads to poor tissue penetration for solid tumors, and hinders the binding of inside antigenic epitopes and the internalization of antibody-conjugated drugs. 7,8 However, several defects deter the further application of antibodies. Antibodies can recognize biomarkers on cell surfaces, thereby activating immune responses or suppressing protumoral biological activities. 5,6 Generally, antibodies are large size proteins, which comprise two pairs of heavy and light chains that form a stable Y-shape structure via disulfide bond linking. Monoclonal antibodies against tumor markers are the most widely investigated targeting elements for precise cancer diagnosis and treatment. 1 To deal with these issues, precision medicine using multi-omics information analyses has been proposed to identify the crucial tumor markers for classifying patients and tailoring precisely targeted treatments. Traditional cancer treatments were designed as one-size-fits-all approaches however, not all patients benefited from the same method owing to inter- and intra-tumor heterogeneity between individuals. Introduction Cancer is a severe disease that threatens human health. In this review, we focus on the protein scaffold applications in cancer therapy and diagnosis in the last 5 years, and discuss the pros and cons, and strategies of optimization and design. To date, more than 20 types of protein scaffolds have been developed, with the most frequently used being affibody, adnectin, ANTICALIN®, DARPins, and knottin. Given the properties of small size, high affinity, and excellent specificity and stability, protein scaffolds have been applied in basic research, and preclinical and clinical fields over the past two decades. By combining robust gene engineering and phage display techniques, libraries with sufficient diversity could be established for target binding scaffold selection. Protein scaffolds are small monomeric proteins with stable tertiary structures and mutable residues, which emerged in the 1990s. These issues have led scientists to explore and develop novel antibody alternatives. Although antibodies are well developed and widely used in cancer therapy and diagnostic fields, some defects remain, such as poor tissue penetration, long in vivo metabolic retention, potential cytotoxicity, patent limitation, and high production cost.
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