Engineered antibody Fc variants with enhanced effector function.

By G. A. Lazar, W. Dang, S. Karki, O. Vafa, Judy S. Peng, L. Hyun, Cheryl Y Chan, H. S. Chung, Araz Eivazi, S. Yoder and 4 more. 2006

805 citations recorded by the source corpus.

Subfields: Molecular Biology, Oncology, Radiology, Nuclear Medicine and Imaging

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Citations in the corpus

Outcome of a Workshop on Applications of Protein Models in Biomedical Research (2009, methodology): “Similar techniques have been used to engineer smaller antibody fragments with improved specificity, affinity, and half-life (Hinton et al., 2004; Lazar et al., 2006; Lippow et al., 2007).”
Energy functions in de novo protein design: current challenges and future prospects. (2013, background): “This promise, however, is still unfulfilled largely because of the low success rate of de novo design (12, 34, 63, 72, 109).”
Achievements and Challenges in Computational Protein Design. (2017, background): “designed antibody Fc variants with enhanced Fcγ-receptor-mediated effector function [59].”
Tumor-associated and microbial proteases compromise host IgG effector functions by a single cleavage proximal to the hinge (2009, methodology): “tion binding assays were adapted from previously reported conditions (47) (see SI”
Therapeutic antibodies for autoimmunity and inflammation (2010, background): “One such mutant, Ser239Asp:Glu330Leu:Ile332Glu, gave a ∼100-fold increase in ADCC potency, with greater maximal target cell killing in some case”
Comparing antibody and small-molecule therapies for cancer (2006, methodology): “To increase FcγR-mediated ADCC activity, the amino-acid sequence or glycosylation of the C H 2 region of mAbs has been manipulated by computational design or mutational analysis to improve its interaction with FcγR”
Potential energy functions for protein design. (2007, background): “[43] optimized the Fc region of an antibody to bind more tightly to the Fc receptor.”
Therapeutic antibodies: successes, limitations and hopes for the future (2009, positive): “A way to increase the efficiency of therapeutic antibodies would be to increase their binding to activating receptors, namely FcgRI, FcgRIIa and more importantly FcgRIIIa, and decrease their interaction with inhibitory FcgRIIb receptors (Shields et al., 2001; Lazar et al., 2006; Desjarlais et al., 2”
Potent antibody therapeutics by design (2006, methodology): “More recently, computational design methods have been used to tailor the interaction between IgG molecules and various FcγRs to modulate effector functions, achieving a more than 100-fold increase in the potency of ADCC elicited by alemtuzumab and trastuzumab variants, as well as increases in the pe”
Antibodies and cancer therapy: versatile platforms for cancer immunotherapy (2010, background): “Efforts to modify the Fc domain primary structure using computational and high-throughput screening have resulted in Fc domains with higher affinity for FcγRIIIA and an enhancement of ADC”
Fcγ receptors as regulators of immune responses (2008, background): “With the availability of antibody variants with enhanced binding to either activating or inhibitory FcγRs, however, it might become possible to integrate an additional activating or inhibitory second signal into the antibody–antigen fusion protei”
Direct prediction of profiles of sequences compatible with a protein structure by neural networks with fragment‐based local and energy‐based nonlocal profiles (2014, background): “However, existing scoring functions for protein design are not yet accurate enough to produce high success rates 12–16 .”
Engineered Protease-resistant Antibodies with Selectable Cell-killing Functions* (2013, methodology): “For these reasons, one common goal for Fc engineering efforts is to generate Fc variants that demonstrate improved effector functions in patients bearing lower affinity Fc R polymorphisms (35, 74).”
Antibody Structure and Function: The Basis for Engineering Therapeutics (2019, background): “This engineering can also be applied to Fc fusions that comprise toxins, radioactive molecules, chemotherapeutic agents, or nucleic acids for targeted delivery [392].”