Antibody–drug conjugate

[2] ADCs are complex molecules composed of an antibody linked to a biologically active cytotoxic (anticancer) payload or drug.

ADCs combine the targeting properties of monoclonal antibodies with the cancer-killing capabilities of cytotoxic drugs, designed to discriminate between healthy and diseased tissue.

The biochemical reaction that occurs upon attaching triggers a signal in the tumor cell, which then absorbs, or internalizes, the antibody together with the linked cytotoxin.

[6] Their targeting ability was believed to limit side effects for cancer patients and to give a wider therapeutic window than other chemotherapeutic agents, although this promise hasn't yet been realized in the clinic.

[13][14] The European Commission approved Inotuzumab ozogamicin[15] as a monotherapy for the treatment of adults with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia (ALL) on June 30, 2017 under the trade name Besponsa® (Pfizer/Wyeth),[16] followed on August 17, 2017 by the FDA.

[22] In July 2018, Daiichi Sankyo Company, Limited and Glycotope GmbH have inked a pact regarding the combination of Glycotope's investigational tumor-associated TA-MUC1 antibody gatipotuzumab and Daiichi Sankyo's proprietary ADC technology for developing gatipotuzumab antibody drug conjugate.

An antibody–drug conjugate consists of 3 components:[31][32] Many of the payloads for oncology ADCs (oADC) are natural product based [34] with some making covalent interactions with their target.

[50] A stable ADC linker ensures that less of the cytotoxic payload falls off before reaching a tumor cell, improving safety, and limiting dosages.

Linkers are based on chemical motifs including disulfides, hydrazones or peptides (cleavable), or thioethers (noncleavable).

However, MMAE linked to an anti-CD30 monoclonal antibody (cAC10, a cell membrane protein of the tumor necrosis factor or TNF receptor) was stable in extracellular fluid.

[63] The first generation uses linking technologies that conjugate drugs non-selectively to cysteine or lysine residues in the antibody, resulting in a heterogeneous mixture.

This approach leads to suboptimal safety and efficacy and complicates optimization of the biological, physical and pharmacological properties.

The absence of a cell wall allows the addition of non-natural factors to the system to manipulate transcription, translation and folding to provide precise protein expression modulation.