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Antibody drug conjugates:
Delivering the next wave of medicines
Delivering the next wave of medicines
Home / R&D / Next generation therapeutics / Antibody drug conjugate
What are antibody drug conjugates?
Antibody drug conjugates (ADCs) are targeted medicines that aim to deliver chemotherapy agents directly to cancer cells via a linker attached to monoclonal antibody. Here we explain their mechanism of action and potential for novel cancer treatments.
How do ADCs work?
ADCs combine a monoclonal antibody (mAb), which binds to a specific target protein on the surface of cancer cells, with a drug, typically a cytotoxic chemotherapy agent, via a chemical linker.1 After binding to the protein target, the ADC is internalised into the cancer cell where it releases the cytotoxic drug. Unlike conventional chemotherapy, ADCs aim to deliver a drug directly into cancer cells and minimise damage to healthy ones.1
‘Fully human’ mAbs, which have been engineered to contain protein sequences encoded by human immunoglobulin genes, are an ideal delivery platform for ADCs. They are designed to be highly targeted and cell-specific, have a long circulating half-life and offer minimal immunogenicity.1 They bind to specific cell surface antigens, such as those present on cancer cells.
The chemical ‘linkers’ that join together the antibodies and cytotoxic drugs are highly stable to prevent cleaving (splitting) before the ADC enters the tumour. After binding to the protein target on the cell surface, the ADC is internalised into the cancer cell where it releases the cytotoxic drug.1
The anticancer drugs (or ‘payloads’) have an ability to cause cell death through a variety of mechanisms.1
Learn more about antibody drug conjugate therapies’ mechanism of action:
The three components of these biologically active drugs, the monoclonal antibody, the linker and the cytotoxic agent, all play a part in defining the therapeutic potential of the ADC.
The tumour targeting antibody must be precise to recognise the target cell, so that the receptor on the cell surface can mediate the internalisation of the antibody drug conjugate. The stability of the linker plays an important role in ensuring that linkers are only cleaved inside the tumour cell, and the cytotoxic payload needs to be of the right potency to exert its cancer therapy effect.1
At AstraZeneca, we are leveraging our expertise in protein engineering and drug discovery to optimise all aspects of an ADC’s mechanism of action, while using AI powered screening methods to identify clinically relevant targets, which help us match and design each ADC with the biology and sensitivities of specific tumour types.
Our aim is for our ADC portfolio to offer treatment options in a wide range of solid and haematological malignancies. To achieve this, it’s critical we continue to optimise target selection, identify novel payloads, focus on developing new linkers and strive to overcome drug resistance.
Learn more about how antibody drug conjugates aim to cause targeted cancer cell death in this video [1:00]:
Chemotherapy is the cornerstone of cancer treatment because it is able to target all vulnerable cells. At Oncology R&D our aim is to replace traditional chemotherapy by developing potent and precise ADCs, which have the potential to kill tumour cells by targeting them directly, while sparing normal cells.
The technological advancements in developing ADCs are building our confidence in their potential to become the backbone of cancer care. We have limitless possibilities in exploring ADCs as a monotherapy and in combinations with other cancer medicines with potential to bring benefit to a broad population of cancer patients.
Cancer cell targeting: Establishing a portfolio of differentiated ADCs
ADCs are a key part of our Oncology R&D strategy. Our vision is for ADCs to replace chemotherapy and become the backbone for novel cancer combination regimens.
Even within one tumour, cancer tissues – and their cell surfaces – vary greatly. There is recognised need for monoclonal antibodies designed for a wide range of tumour specificity, so that cancer therapies can effectively recognise and target all types of cancer cells, while sparing healthy cells.
We are expanding beyond conventional monotherapy ADCs, which target a single protein on tumour cells, with our multispecific discovery platform capable of targeting two or more target proteins expressed on tumour cells. Multispecific ADCs are highly targeted therapies, that have the potential to improve target selectivity and reduce treatment side effects.1
Leveraging our internal ADC expertise, we are demonstrating the strength of our proprietary platform across several ADCs currently in clinical development. Beyond this, we are also working jointly with several external partners to bring ADCs to patients as quickly as possible and augment our clinical pipeline.
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Reference:
1. Peters C, Brown S. Antibody-drug conjugates as novel anti-cancer chemotherapeutics. Biosci Rep. 2015;35(4):e00225. Published 2015 Jul 14. Available at: http://onlinelibrary.wiley.com/doi/10.1016/j.febslet.2013.10.015/full. Accessed July 2024.
Veeva ID: Z4-66974
Date of preparation: July 2024