Building better monoclonal antibody-based therapeutics

Weiner, George J.

doi:10.1038/nrc3930

Cited by 562 publications

(474 citation statements)

References 115 publications

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“…It is also the main class used in development of antibody therapies, especially those for cancer. 1 IgG is also used to treat immune deficiencies and autoimmune diseases in the form of intravenous immunoglobulin (IVIg), generated from a plasma pool of thousands of donors. 2,3 The working mechanisms, efficacy and safety of immunoglobulin therapies must be investigated in in vivo model systems before they can be studied in human trials.…”

Section: Introductionmentioning

confidence: 99%

“…5,6 Antibody therapies currently in development are usually based on humanized or human antibodies to reduce the possibility of immunogenicity, increase half-life and increase efficacy. 1 Cancer therapies often depend not only on the neutralizing capacity of the antibody's antigen binding fragments (Fabs) to eliminate pathogen or malignant cells, but also rely on interaction of the constant domain (Fragment crystallizable, Fc) with components of the immune system. This involves binding to molecules including C1q, 7 intracellular Fc receptor TRIM21, 8 neonatal Fc receptor FcRn 9 and the family of Fc gamma receptors (FcgRs).…”

Section: Introductionmentioning

confidence: 99%

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Affinity of human IgG subclasses to mouse Fc gamma receptors

Dekkers

Bentlage

Stegmann

et al. 2017

mAbs

185

162

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Human IgG is the main antibody class used in antibody therapies because of its efficacy and longer halflife, which are completely or partly due to FcgR-mediated functions of the molecules. Preclinical testing in mouse models are frequently performed using human IgG, but no detailed information on binding of human IgG to mouse FcgRs is available. The orthologous mouse and human FcgRs share roughly 60-70% identity, suggesting some incompatibility. Here, we report binding affinities of all mouse and human IgG subclasses to mouse FcgR. Human IgGs bound to mouse FcgR with remarkably similar binding strengths as we know from binding to human ortholog receptors, with relative affinities IgG3>IgG1>IgG4>IgG2 and FcgRI>>FcgRIV>FcgRIII>FcgRIIb. This suggests human IgG subclasses to have similar relative FcgRmediated biological activities in mice.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Affinity of human IgG subclasses to mouse Fc gamma receptors

Dekkers

Bentlage

Stegmann

et al. 2017

mAbs

185

162

View full text Add to dashboard Cite

show abstract

“…In addition, stability is important to avoid denaturation and aggregation, not only for long shelf-life and persistent bio-availability, but also because denaturation and aggregation can lead to increased immunogenicity [15,16,17]. Consequently there is still room for improvement in building better antibodies having higher affinity and lower immunogenicity [18].…”

Section: Introductionmentioning

confidence: 99%

abYsis: Integrated Antibody Sequence and Structure—Management, Analysis, and Prediction

Swindells¹,

Porter

Couch

et al. 2017

Journal of Molecular Biology

145

134

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abYsis is a web-based antibody research system that includes an integrated database of antibody sequence and structure data. The system can be interrogated in numerous ways -from simple text and sequence searches to sophisticated queries that apply 3D structural constraints. The publicly available version includes pre-analysed sequence data from EMBL-ENA and Kabat as well as structure data from the PDB. A researcher's own sequences can also be analysed through the web interface.A defining characteristic of abYsis is that sequences are automatically numbered with a series of popular schemes such as Kabat and Chothia and then annotated with key information such as CDRs and potential post-translational modifications. A unique aspect of abYsis is a set of residue frequency tables for each position in an antibody, allowing 'unusual residues' (those rarely seen at a particular position) to be highlighted and decisions to be made on which mutations may be acceptable. This is especially useful when comparing antibodies from different species.

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“…Many studies have shown the effectiveness of all these agents in the transplant recipients but no standardized practice has been established to date advocating superiority of one agent over the other thus every center has its own protocols based on their experience 38 . These agents are an integral part of transplant medications and often combination regimens are used to achieve success both short term and long term and these agents are mandatory to use when performing transplantation across the borders like HLA and ABO incompatible individuals 39 .…”

Section: And18mentioning

confidence: 99%

The Anti-thymocyte Globulin use makes kidney transplantation journey smooth

Mahmood¹,

Ahmed²,

Aqeel³

et al. 2018

Int. j. endorsing health sci. res.

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Background: The most common immunosuppressant, Anti-thymocyte Globulin (ATGs) has been widely used by clinicians for the treatment and prevention of rejection at the time of organ transplant. Transplantation is the best option for the people with renal failure at end stage, requiring replacement of renal therapy. This is a promising treatment option with significant benefits in terms of mortality and morbidity. ATG prevents organ rejection by inhibition of activated T-cells and other immune and nonimmune cells. The aim of the study was to compare different induction regimens with ATG for the survival of smooth kidney transplantation. Methodology: Studies of the last 20 years, focusing on kidney transplantation and the efficacy of antithymocyte use for kidney transplantation were reviewed for the study literature. The keywords used were Kidney Transplantation, Induction agents, ATG, Allograft, Immunosuppressant Agents. Results: Literature suggested that the most important problem with transplantation is the protection of the allograft from activated immunological forces, which begin to react early in the period after transplantation and cause significant damage with serious short-term and long-term consequences. This process is called rejection, which is usually classified as cell-mediated and antibody-mediated rejection. The phenomenon mediated by cells causes concern, as it is the cause of future failures and damage to the allograft. To combat these phenomena with different results, various strategies were adopted. Among these therapies, ATG has recognized the exceptional importance of preventing cellular mediated rejection, allowing allotransplants to function smoothly with the greatest possible long-term benefits. Conclusion: It can be concluded on the basis of previous studies that ATG as an induction agent, is more efficient in reducing the rejection rate in the renal transplantation as compared with other agents.

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Building better monoclonal antibody-based therapeutics

Cited by 562 publications

References 115 publications

Affinity of human IgG subclasses to mouse Fc gamma receptors

Affinity of human IgG subclasses to mouse Fc gamma receptors

abYsis: Integrated Antibody Sequence and Structure—Management, Analysis, and Prediction

The Anti-thymocyte Globulin use makes kidney transplantation journey smooth

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