Advancements in cancer therapy: The revolutionary role of antibody-drug conjugates

Sponsored Content by Sino Biological Inc.May 14 2024Reviewed by Maria Osipova The emergence of antibody-drug conjugates has seen them become a promising class of anticancer therapeutics, exhibiting better precision and reduced off-target toxicity in targeting cancer cells.1

Mechanism of action ADCs target cancer cells with enhanced precision and limited off-target toxicity in comparison to traditional chemotherapy agents. The mechanism involves the binding of a monoclonal antibody to an overexpressed target antigen on cancer cells, which leads to internalization and formation of endosomes.

ADC building blocks An ADC is made up of a target-specific mAb, a cytotoxic payload, and a chemically synthesized linker that covalently connects the toxin to the antibody.4,6,7 The mAb attaches to certain antigens on the tumor cell surface, and ADCs are internalized into tumor cells during the formation of antibody-antigen complexes.1,3

Common ADC targets include HER2, Trop2, Nectin4, EGFR, CD19, CD22, CD33, CD30, BCMA, and CD79b.1,3,4,7,9 Featured hematological malignancy target protein from Sino Biological Human CD22/Siglec-2 Protein, HPLC-verified Binding assay: Immobilized anti-CD22 antibody can bind human Siglec-2/CD22 protein. Image Credit: Sino Biological Inc

Cytotoxic payload No more than 2% of ADC administered reaches the tumors targeted.5 Therefore, sufficiently high potency is crucial for ADC payload compounds.5 Tubulin inhibitors and DNA damaging agents are among the current cytotoxic payloads.1,7,11 Linker Cleavable and non-cleavable linkers can be leveraged to control the release of the cytotoxic payload.3,4 Cleavable linkers take advantage of the environmental differences between circulation and tumor cells, using chemical cleavage 4,9 or enzyme cleavage .1,9

This may lead to an unstable scenario, which can cause early payload release, off-target toxicity, and harm the chances of retaining consistency.3,7 Comparatively, site-specific conjugation is dependent on cysteine-based coupling, revealing disulfide bonds for a controlled approach and limiting any chance of heterogeneity.1,5 However, it can undermine antibody integrity.1

To face these challenges head-on, next-generation ADCs are centered on the optimization of monoclonal antibodies, linkers, and payloads, leveraging bispecific antibody technology, and utilizing dual-payload ADCs.1,4,5

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