Composite Antibody Humanisation | Abzena

Composite Human Antibodies™

Antibody Humanisation and Deimmunisation Platform

shutterstock_143646112An unwanted immune response can lead to treatment failure

The goal of humanisation is to make foreign or non-human antibodies appear ‘human’ to the immune system so that they do not raise antibodies against the drug (anti-drug antibodies or ADAs). ADAs can potentially lead to reduced efficacy through rapid clearance or neutralisation of the drug, or toxicity due to cross-reaction with proteins in the body, which can have catastrophic consequences for the patient.

The key drivers of immunogenicity are T cell epitopes which activate CD4+ T cells that, in turn, help B cells to develop ADAs. Standard antibody humanisation techniques do not remove T cell epitopes so some of the humanised and fully human antibodies that have been developed have caused unwanted immune responses in patients.

Antibodies are humanised and deimmunised to reduce the risk of immunogenicity

Abzena has pioneered a two-pronged approach to antibody engineering to reduce immunogenicity using its Composite Human Antibody™ technology. The approach combines the best elements of humanisation and deimmunisation to create fully human antibodies that are also devoid of T cell epitopes.

From any starting antibody (e.g. murine, rat or rabbit), Composite Human Antibodies™ are built using multiple sequence segments derived from variable regions of unrelated human antibodies as building blocks. Through careful analysis of the binding domains, selection of appropriate human sequence segments and the application of in silico tools, humanised antibody sequences are combined to create a fully functional antibody devoid of T cell epitopes. We also test the lead Composite Human Antibody™ in our EpiScreen™ ex vivo immunogenicity assay to confirm that the antibody has reduced potential for an adverse immune response in patients. In addition to removing T cell epitopes, we can also analyse your molecule for potential sequence liabilities and incorporate risk mitigation strategies into the design phase of the humanised antibodies.

Matching the binding affinity of the starting antibody is just the first step

Composite Human Antibodies™ are carefully designed to ensure the affinity and specificity of the parent antibody are maintained. Standard binding assays such as using ELISA and/or Biacore Surface Plasmon Resonance are built into every antibody humanisation program and other assays, e.g. looking at thermal stability using Sypro Orange, can be included. We also have a suite of biological assays available, or can develop an assay, to check that the functionality of the humanised antibody has been retained.

Composite Human Antibodies™ are in clinical development for a range of conditions

Abzena has completed over 100 antibody humanisation projects for a diverse array of partners from academia to industry with many, confident in our ability to deliver, returning more than once. Twelve antibodies humanised using our Composite Human Antibody™ technology are being progressed through various stages of clinical development by our partners.

shutterstock_143646112Working with Abzena

Abzena’s services are tailored for each project to ensure that the objectives are met or exceeded. Experienced project teams are assigned to each study focusing on progressing projects through to results in the minimum amount of time. Our clients widely regard us as professional and attentive partners who deliver quality results.

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