A View On Antibody-Drug Conjugates

Antibody-drug Conjugates: Next-Generation of Targeted Cancer Treatments
Iwan Bertholjotti and Lawrence Bonnafoux from Lonza give an insider look at how these promising treatments make it from development to commercialization.

Chemotherapy is the first-line treatment for most types of cancer. However, one of the major challenges with this approach is that it targets both cancer and healthy cells, with patients suffering severe side effects. A new class of therapies, called antibody-drug conjugates, or ADCs, can target tumors much more precisely by harnessing the power of antibodies. The antibody can bind specific types of tumor cells, delivering a fatal blow to the cancer cells while sparing healthy cells. These promising new drugs have seen a significant uptick in FDA approvals in recent years, pointing towards a trend that could transform the way many diseases are treated.

While numerous companies succeed in developing promising ADCs, manufacturing such complex and highly potent treatments presents unique challenges. The intricacy of scaling up the manufacturing of ADCs leads many companies to outsource their production, and Lonza currently fabricates the majority of ADC therapeutics in the world. For the companies that choose to work with Lonza, the collaboration simplifies the process and streamlines the supply chain. Decades of collective experience in fabricating ADCs means that the drugs make it from discovery to approval in less time, improving patients' lives through more effective, targeted treatments with fewer side effects.

Curious to Know More?
Listen to the conversation between A View On host Martina Hestericová and two of Lonza’s experts on ADC manufacturing—Lonza’s senior director of Commercial Development of bioconjugates, Iwan Betholjotti, and Lawrence Bonnafoux, Lonza’s Head of MSAT BioConjugates.

KEY TERMS IN CONTEXT:

Bioconjugates are a class of biopharmaceuticals developed by attaching two molecules together, of which at least one is a biomolecule. Examples of bioconjugates include antibody-drug conjugates (ADCs), PEGylated proteins, and vaccine conjugates.

Antibody-drug conjugates consist of three parts: an antibody, a cytotoxic drug and the linker that covalently binds these two together. This approach combines the targeted delivery of the antibody with the cancer-killing power of the cytotoxic drug that would be too potent to be used on its own.

A cytotoxic drug is a drug that contains a molecule toxic to cells, leading to cellular death. Used in traditional chemotherapy, these molecules attack both healthy and cancerous cells. When linked to an ADC antibody, they target only the tumor.

Targeted delivery of a cytotoxin is when a cell-killing toxin is delivered to a specific type of cell, such as tumor cells. This specificity allows for effective cancer treatment with fewer unwanted side effects for the patient.

Scaling-up production for bioconjugates involves moving from manufacturing small batches for clinical trials to large batches up to five kilograms for commercial production. This major challenge for companies is essential for the successful commercialization of ADCs.