#20 Silence is golden: The importance of attenuating effector functions in therapeutic antibodies (On Demand)

Antibodies are nature’s pro-drugs, wonderfully evolved to target pathogens and activate immune systems. For certain indications where ADCC or CDC are required this is ideal, but for many other applications activation of inflammatory responses is unnecessary and potentially highly undesirable. In these situations silenced antibodies with either naturally low effector function or engineered Fc domains are the preferred option. However, many of the commonly used options in the clinic, such as IgG4, LALA or aglycosylation, are widely reported to still have residual Fc receptor binding and cytokine activation in patients.

This presentation will describe the first thorough comparison of most of the generic and proprietary Fc silencing mutations, demonstrating that all previously reported variants show residual binding to Fc receptors. It will also describe the discovery of a novel set of mutations, known as STR, that show no detectable binding to Fcγ receptors and do not elicit inflammatory cytokine responses. Meanwhile, immunogenicity, stability and PK are unaffected. This totally silenced variant has the potential to improve the safety and efficacy of therapeutic antibodies and Fc fusion proteins.

Seminar Information
Date Presented:
April 28, 2022 11:00 AM Eastern
Length:
1 hour
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Silence is golden: The importance of attenuating effector functions in therapeutic antibodies

Antibodies are nature’s pro-drugs, wonderfully evolved to target pathogens and activate immune systems. For certain indications where ADCC or CDC are required this is ideal, but for many other applications activation of inflammatory responses is unnecessary and potentially highly undesirable. In these situations silenced antibodies with either naturally low effector function or engineered Fc domains are the preferred option. However, many of the commonly used options in the clinic, such as IgG4, LALA or aglycosylation, are widely reported to still have residual Fc receptor binding and cytokine activation in patients.

This presentation will describe the first thorough comparison of most of the generic and proprietary Fc silencing mutations, demonstrating that all previously reported variants show residual binding to Fc receptors. It will also describe the discovery of a novel set of mutations, known as STR, that show no detectable binding to Fcγ receptors and do not elicit inflammatory cytokine responses. Meanwhile, immunogenicity, stability and PK are unaffected. This totally silenced variant has the potential to improve the safety and efficacy of therapeutic antibodies and Fc fusion proteins.

Speaker Information
Ian Wilkinson  [ view bio ]
Individual topic purchase: Selected