Phage Display Derived Monoclonal Antibodies: From Bench to Bedside

Alfaleh, Mohamed A.; Alsaab, Hashem O.; Mahmoud, Ahmad Bakur; Alkayyal, Almohanad A.; Jones, Martina L.; Mahler, Stephen M.; Hashem, Anwar M.

doi:10.3389/fimmu.2020.01986

Cited by 195 publications

(131 citation statements)

References 548 publications

(254 reference statements)

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“…It is essential to design and develop potential antibodies which target SARS-CoV-2 specifically and selectively ( Table 2 ). The human phage display technology is a powerful tool that has revolutionized the development of identifying and optimizing antibodies, providing breakthrough points for further applications in the invention of therapeutic mAbs in anti-infectious diseases ( Alfaleh et al, 2020 ).…”

Section: Antibodies Exclusively Target Sars-cov-2 Rbdmentioning

confidence: 99%

Antibodies and Vaccines Target RBD of SARS-CoV-2

Min

Sun

2021

Front. Mol. Biosci.

142

106

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The novel human coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which gives rise to the coronavirus disease 2019 (COVID-19), has caused a serious threat to global public health. On March 11, 2020, the WHO had officially announced COVID-19 as a pandemic. Therefore, it is vital to find effective and safe neutralizing antibodies and vaccines for COVID-19. The critical neutralizing domain (CND) that is contained in the receptor-binding domain (RBD) of the spike protein (S protein) could lead to a highly potent neutralizing antibody response as well as the cross-protection of other strains of SARS. By using RBD as an antigen, many neutralizing antibodies are isolated that are essential to the therapeutics of COVID-19. Furthermore, a subunit vaccine, which is based on the RBD, is expected to be safer than others, thus the RBD in the S protein is a more important target for vaccine development. In this review, we focus on neutralizing antibodies that are targeting RBD as well as the vaccine based on RBD under current development.

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Section: Antibodies Exclusively Target Sars-cov-2 Rbdmentioning

confidence: 99%

Antibodies and Vaccines Target RBD of SARS-CoV-2

Min

Sun

2021

Front. Mol. Biosci.

142

106

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“…Antibodies exhibit a versatile range of molecular recognition properties that make them cornerstones of therapeutics, diagnostics, and basic research tools. [1][2][3][4][5][6][7][8][9] The rise of display technologies such as yeast and phage display has greatly expanded the range of methods for antibody discovery, characterization, and engineering. 1,[10][11][12] In addition to facilitating new approaches to mining antibody repertoires from immunologically derived sources, [13][14][15][16] display technologies have led to the establishment of powerful, laboratory designed synthetic antibody libraries.…”

Section: Introductionmentioning

confidence: 99%

Chemical Diversification of Simple Synthetic Antibodies

et al. 2021

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Antibodies possess properties that make them valuable as therapeutics, diagnostics, and basic research tools. However, antibody chemical reactivity and covalent antigen binding are constrained, or even prevented, by the narrow range of chemistries encoded in the canonical amino acids. In this work, we investigate strategies for leveraging an expanded range of chemical functionality to augment antibody binding properties. Using yeast displayed antibodies, we explored the presentation of noncanonical amino acids (ncAAs) in or near antibody complementarity determining regions (CDRs) and evaluated the properties of the resulting constructs. To enable systematic characterization of ncAA incorporation sites, we first investigated whether diversification of a single antibody loop would support isolation of binding clones. We constructed a billion-member library containing canonical amino acid diversity and loop length diversity only within the 3rd complementarity determining region of the heavy chain (CDR-H3). Screens against a series of immunoglobulins from three species resulted in the isolation of antibodies exhibiting moderate affinities (double-to triple-digit nanomolar affinities) and, in several cases, single-species specificity. These findings confirmed that antibody specificity can be mediated by a single CDR. With this constrained diversity, we were able to utilize additional CDRs for the installation of chemically reactive and photo-crosslinkable ncAAs. Apparent binding affinities of ncAA-substituted synthetic antibodies on the yeast surface revealed that ncAA incorporation is generally well tolerated. However, changes in binding affinities did occur upon substitution, and varied based on factors including ncAA side chain identity, location of ncAA incorporation, and the ncAA incorporation machinery used. We further investigated chemical modifications facilitated by ncAA installation. Multiple azide-containing ncAAs supported both copper-catalyzed azide-alkyne cycloaddition (CuAAC) and strain-promoted azide-alkyne cycloaddition (SPAAC) without abrogation of binding function following the installation of bulky probes. Similarly, several alkyne substitutions facilitated CuAAC without apparent disruption of binding function. Finally, antibodies substituted with a photo-crosslinkable ncAA were evaluated for ultraviolet-mediated crosslinking on the yeast surface. Competition-based assays revealed position-dependent linkages that could not be displaced by excess soluble antigen, strongly suggesting successful crosslinking. Key findings regarding CuAAC reactions and photo-crosslinking on the yeast surface were confirmed using soluble forms of ncAA-substituted clones. These consistent behaviors between the yeast surface and in solution suggest that chemical diversification can be incorporated into yeast display screening approaches. Taken together, our results highlight the power of integrating the use of yeast display and ncAAs in search of proteins with "chemically augmented" binding functions. More specifically, o...

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“…The US FDA has approved several antiangiogenic agents for cancer treatment; these include monoclonal antibodies [40] that target specific proangiogenic growth factors and their receptors (ramucirumab and bevacizumab), tyrosine kinases inhibitors (TKIs; axitinib, sunitinib, sorafenib, regorafenib, cabozantinib, pazopanib, and vandetanib) and inhibitors of mammalian target of rapamycin (mTOR; everolimus and temsirolimus). Despite their availability, many of these agents have limited clinical uses [41].…”

Section: Clinical Trials In Antiangiogenic Therapeuticsmentioning

confidence: 99%

Nanomaterials for Antiangiogenic Therapies for Cancer: A Promising Tool for Personalized Medicine

Alsaab

Al-Hibs

Alzhrani

et al. 2021

IJMS

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Angiogenesis is one of the hallmarks of cancer. Several studies have shown that vascular endothelium growth factor (VEGF) plays a leading role in angiogenesis progression. Antiangiogenic medication has gained substantial recognition and is commonly administered in many forms of human cancer, leading to a rising interest in cancer therapy. However, this treatment method can lead to a deteriorating outcome of resistance, invasion, distant metastasis, and overall survival relative to its cytotoxicity. Furthermore, there are significant obstacles in tracking the efficacy of antiangiogenic treatments by incorporating positive biomarkers into clinical settings. These shortcomings underline the essential need to identify additional angiogenic inhibitors that target numerous angiogenic factors or to develop a new method for drug delivery of current inhibitors. The great benefits of nanoparticles are their potential, based on their specific properties, to be effective mechanisms that concentrate on the biological system and control various important functions. Among various therapeutic approaches, nanotechnology has emerged as a new strategy for treating different cancer types. This article attempts to demonstrate the huge potential for targeted nanoparticles and their molecular imaging applications. Notably, several nanoparticles have been developed and engineered to demonstrate antiangiogenic features. This nanomedicine could effectively treat a number of cancers using antiangiogenic therapies as an alternative approach. We also discuss the latest antiangiogenic and nanotherapeutic strategies and highlight tumor vessels and their microenvironments.

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Phage Display Derived Monoclonal Antibodies: From Bench to Bedside

Cited by 195 publications

References 548 publications

Antibodies and Vaccines Target RBD of SARS-CoV-2

Antibodies and Vaccines Target RBD of SARS-CoV-2

Chemical Diversification of Simple Synthetic Antibodies

Nanomaterials for Antiangiogenic Therapies for Cancer: A Promising Tool for Personalized Medicine

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