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How the Next Generation Antibody Drug Conjugates Expands Beyond Cytotoxic Payloads for Cancer Therapy

Antibody-drug Conjugates or ADCs combine the selectivity of antibodies with the efficacy of small molecule drugs, allowing for more precise, targeted, therapeutic applications.

Combining the advantages of antibodies in binding a specific target with the capabilities of a therapeutic payload, the majority of ADCs in preclinical and clinical development are for indications in oncology and hematology, where the cytotoxic payloads linked to antibodies are targeting antigen-expressing cancer cells.[1]

Over the last two decades, researchers have also explored opportunities to develop ADCs beyond cancer, into other disease indications including autoimmune disease, difficult-to-treat bacterial infections, and atherosclerosis.

However, to succeed in the development of these non-oncologic ADCs, a number of challenges need to be resolved in order to fulfill the larger promise of ADC technology.

In an article published in Methods in Molecular Biology, Michael J. McPherson and Adrian D Hobson at Abbvie Global Biologics, AbbVie Bioresearch Center, Worcester, MA, USA, demonstrate that the modulation of pathogenic cellular activity via ADC-mediated delivery of bioactive small molecules is indeed an attractive concept for non-oncology indications. And in the article, McPherson and Hobson explore a variety of payload mechanisms beyond cell killing, from early in vitro proof-of-concept experiments to clinical trials. [2]

With a growing understanding of ADC-technology, it’s only predictable that the development of these compounds in therapeutics areas for diseases outside the realm of oncology and hematology will rapidly increase.  Some of these novel ADCs will be developed with curative intent, some as a precursor or conditioning to further therapies.

Read the full peer-review article on ADC Review, Journal of Antibody-drug Conjugates.