Mutating Antibodies for Easier Drug-Conjugate Manufacturing

Scientists in the United States have developed a general-purpose antibody that they hope will help revolutionize antibody-drug conjugate (ADC) manufacturing. The team, from Johns Hopkins University, says they mutated the fragment crystallizable (FC) region, the part of an antibody that modulates immune response. The aim was to create new sites to attach molecules, including nanoparticle drugs or fluorescent markers for quality assurance.

According to Jamie Spangler, PhD, associate professor of biomedical engineering and chemical & biomolecular engineering, the new antibodies could—in the future—lead to more effective and easier-to-manufacture drug conjugates.

“The chemistry of antibody drug conjugates is so heterogeneous. It can be hard to characterize the drug-to-antibody ratio and to [do things like] maintain consistency in formulations.”

To get around this problem, Spangler’s team installed six mutations on the FC region of an antibody that can act as attachment sites for a variety of molecules. The team was able to attach a dye to quantify how many sites were available and discovered the best productivity was found when using up to four sites.

They emphasize that the sites can be used for many purposes.

“You can attach whatever you want,” Spangler explains. “You could use [them] to make an antibody-dye conjugate or even a drug conjugate.”

According to Spangler, the team has already shown that the mutations can be used to conjugate with nanoparticles. “We encapsulate the protein we want to deliver within the nanoparticle, and then we coat the surface with an antibody. The nanoparticle we’re carrying, in this case, contains some GFP [green fluorescent protein], which is a fluorescent readout, but we can attach that to an antibody.”

After the antibody binds to a cell expressing the target, it’s internalized, and the nanoparticle can release its cargo, she explains. This system can be used for any number of purposes.

“The sky’s the limit for how people want to use this in their own research and their own work,” she says. “It’s a fully tuneable and generalisable system, and we’d encourage people to think broadly and creatively about the different attachments they can use.”

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