Alteration of Electrostatic Surface Potential Enhances Affinity and Tumor Killing Properties of Anti-ganglioside GD2 Monoclonal Antibody hu3F8

Zhao, Qi; Ahmed, Mahiuddin; Guo, Hong-Fen; Cheung, Irene Y.; Cheung, Nai‐Kong V.

doi:10.1074/jbc.m115.650903

Cited by 30 publications

(21 citation statements)

References 37 publications

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“…This suggests that flexibility and affinity are not directly linked in the 3F8 antibody. Other mechanisms proposed for increased antigen affinity include changes in electrostatic surface potential (Zhao et al, 2015) or increased buried hydrophobic surface area with antigen binding. We calculated the molecular hydrophobic potential based on the surface projection of atomic logP values (Ghose et al, 1998; Steinkellner et al, 2009), along with the surface electrostatic potential and saw no large charges in 3F8 between the germline and affinity mature structures (Figure 6E–H).…”

Section: Resultsmentioning

confidence: 99%

Therapeutic Antibodies to Ganglioside GD2 Evolved from Highly Selective Germline Antibodies

et al. 2017

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Summary Antibodies play a crucial role in host defense and are indispensable research tools, diagnostics, and therapeutics. Antibody generation involves binding of genomically encoded germline antibodies followed by somatic hypermutation and in vivo selection to obtain antibodies with high affinity and selectivity. Understanding this process is critical for developing monoclonal antibodies, designing effective vaccines, and understanding autoantibody formation. Prior studies have found that antibodies to haptens, peptides, and proteins evolve from polyspecific germline antibodies. The immunological evolution of antibodies to mammalian glycans has not been studied. Using glycan microarrays, protein microarrays, cell binding studies, and molecular modeling, we demonstrate that therapeutic antibodies to the tumor-associated ganglioside GD2 evolved from highly specific germline precursors. The results have important implications for developing vaccines and monoclonal antibodies that target carbohydrate antigens. In addition, they demonstrate an alternative pathway for antibody evolution within the immune system that is distinct from the polyspecific germline pathway.

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Section: Resultsmentioning

confidence: 99%

Therapeutic Antibodies to Ganglioside GD2 Evolved from Highly Selective Germline Antibodies

et al. 2017

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“…Previously, we successfully used yeast display for further maturation of antibodies because it allows fine discrimination between mutants by flow cytometry (57,61). A mutant yeast library of relatively large (up to 10 8 ) size was generated and subjected first to a preselection by using biotinylated B7-H3-mFc-conjugated magnetic beads, allowing elimination of yeast cells that did not express antibodies or bound weakly to antigen.…”

Section: Resultsmentioning

confidence: 99%

Humanized Affinity-matured Monoclonal Antibody 8H9 Has Potent Antitumor Activity and Binds to FG Loop of Tumor Antigen B7-H3

Ahmed

Cheng

Zhao

et al. 2015

Journal of Biological Chemistry

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Background: B7-H3 is an immune inhibitory ligand and an antigen on many solid tumors. Results: Antibody 8H9 was humanized and affinity-matured, and its epitope was mapped to the FG loop of B7-H3. Conclusion: hu8H9 antibodies had potent antitumor activity and may modulate immune inhibitory properties of B7-H3. Significance: Antibodies were developed to target solid tumors and affect immune checkpoint blockade.

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“…Computational simulation of antibody-antigen complexes has been used to guide the design of therapeutic antibodies [54][55][56]. Numbers of antibody structures (currently around 2,000 depositions) are available in the Protein Data Bank [PDB].…”

Section: Perspectives On the Development Of Neutralizing Antibodies Amentioning

confidence: 99%

Perspectives on therapeutic neutralizing antibodies against the Novel Coronavirus SARS-CoV-2

Zhou¹,

Zhao²

2020

Int. J. Biol. Sci.

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257

240

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A newly identified novel coronavirus (SARS-CoV-2) is causing pneumonia-associated respiratory syndrome across the world. Epidemiology, genomics, and pathogenesis of the SARS-CoV-2 show high homology with that of SARS-CoV. Current efforts are focusing on development of specific antiviral drugs. Therapeutic neutralizing antibodies (NAbs) against SARS-CoV-2 will be greatly important therapeutic agents for the treatment of coronavirus disease 2019 . Herein, the host immune responses against SARS-CoV discussed in this review provide implications for developing NAbs and understanding clinical interventions against SARS-CoV-2. Further, we describe the benefits, challenges and considerations of NAbs against SARS-CoV-2. Although many challenges exist, NAbs still offer a therapeutic option to control the current pandemic and the possible re-emergence of the virus in the future, and their development therefore remains a high priority.

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Alteration of Electrostatic Surface Potential Enhances Affinity and Tumor Killing Properties of Anti-ganglioside GD2 Monoclonal Antibody hu3F8

Cited by 30 publications

References 37 publications

Therapeutic Antibodies to Ganglioside GD2 Evolved from Highly Selective Germline Antibodies

Therapeutic Antibodies to Ganglioside GD2 Evolved from Highly Selective Germline Antibodies

Humanized Affinity-matured Monoclonal Antibody 8H9 Has Potent Antitumor Activity and Binds to FG Loop of Tumor Antigen B7-H3

Perspectives on therapeutic neutralizing antibodies against the Novel Coronavirus SARS-CoV-2

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