Page 16 - Tyrosine-Based Bioconjugations - Jorick Bruins

Chapter 1
trispecific antibody, generating a [2]:1:1 format (Figure 3A).24 Of note, trispecific antibodies are antibodies that bind to three different targets, whereas trifunctional antibodies are antibodies that have three different functionalities. Functionalities can also include conjugated drugs, radiolabels, cytokines, and fluorophores (Figure 3B).
Figure 3. (A) Knob-in-hole antibody with two distinct scFv fused, generating a [2]:1:1 antibody format. (B) Trifunctional antibody with two scFvs fused to the light chain and two other functionalities on the heavy chains, generating a [2]:2:2 antibody format.
1.1.3. Antibody conjugates
Besides the expression of new functionalities to an antibody via fusion of an additional protein fragments through its termini, (non-natural) functionalities can also be imparted post- recombinantly with a variety of conjugation methods. Via a wide array of chemical andenzymatic methods, functionalities such as fluorescent markers, highly potent cytotoxic agents, radioactive isotopes, and proteins can be introduced in a modular fashion, with potential application in the field of diagnostics,25 imaging,26-28 or therapeutics.28, 29 Notable examples include fluorescent groups or radionuclides on antibodies, allowing cancer cells to be reliably imaged with high sensitivity to provide real-time information regarding cancer screening, staging and treatment.26- 28 Additionally, tumor-specific fluorescent antibodies can greatly aid in surgical procedures with regards to detecting and removing tumors.25, 26
Common antibody derivatives with therapeutic applications are antibody-drug conjugates (ADCs)29, 30 and radiolabeled antibodies.28 Radiolabeled antibodies are radionuclides with a half- life of a few days conjugated to a tumor-targeting antibody, where the affinity of the antibody results in build-up of radionuclide and therefore localized radiation-treatment. Where radiolabeled antibodies are the localized version of radiation treatment, ADCs are the localized
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