“The results were extraordinary,” says Fleishman. “Without any additional adjustments to the proposed designs, the humanized antibodies functioned just as effectively as the mouse’s original.” Tests of four other antibodies, all designed with CUMAb, were just as impressive, and sometimes even surpassed the original animal antibody’s activity or stability.
CUMAb is a powerful new tool that could significantly accelerate the design of new antibody-based drugs, as well as lower development costs. Fleishman and his team have turned the algorithm into a web server that any academic can use. “This is the first time that a method has shown such broad success in this critical biomedical engineering problem. It is quite likely to become a key element in accelerating the transition from therapeutic candidate molecules to real-world drugs,” says Fleishman.
The new approach to humanizing antibodies might be applied to other issues in therapeutic antibody engineering. For example, many antibody formulations tend to be highly viscous, and they have to be diluted before use. These are then administered through infusion, and it can take hours to get enough of the antibody into the bloodstream. With a computer program that yields a number of viable antibodies, researchers might be able to choose some that require less dilution or have other properties that make them easier or more comfortable to administer, improving outcomes for patients.
“We hope that CUMAb, now accessible online, will empower researchers and professionals to develop antibodies more swiftly and accurately,” says Tennenhouse.