Cancer-fighting antibodies with a one-two punch take aim at tumours

Cancer-fighting drugs called bispecific antibodies are having a moment. A growing number are making their way into the clinic, and researchers are developing increasingly elaborate molecules with new capabilities.

In the past five years, the number of bispecific antibodies — which can bind to two targets at the same time — approved by global regulators has grown from 3 to more than 20, says Christian Klein, who developed drugs at pharmaceutical company Roche in Basel, Switzerland, and is now launching his own biotechnology firm. The drugs generated US$18 billion in sales in 2025, he says.

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“Bispecifics have really kind of exploded,” says Paul Carter, who develops antibody therapies at Genentech, a biotechnology company in South San Francisco, California. “There are more flavours of bispecifics than Ben and Jerry’s ice cream.”

That success — as well as advances in protein production and artificial intelligence — is spurring efforts to create ‘multispecific’ antibodies that bind to three or more different targets, says Daniel Chen, co-founder and chief executive of Synthetic Design Lab, a biotechnology company in San Carlos, California. At the American Association for Cancer Research Drug Discovery and Development meeting in Boston, Massachusetts, at the end of July, for example, researchers presented multispecific-antibody cancer therapies that could be less toxic to healthy cells, more effective against tumours and better able to counter cancer’s pernicious ability to become resistant to treatment than conventional medicines.

Medicinal multitaskers

Bispecific antibodies were first described more than 50 years ago, but the first treatment was only approved in 2009.

Part of the delay was due to working out how best to produce the molecules in the laboratory, says Jamie Spangler, a bioengineer at Johns Hopkins University in Baltimore, Maryland. Often the process led to antibodies that bound to themselves and one another. “They would all come out as aggregated balls of garbage,” Spangler says. “With better tools and resources for protein production, we can dream up these molecules and make them happen.”

Most of the approved bispecific antibodies bind to both a protein expressed by cancer cells and to immune cells called T cells. Called ‘T cell engagers’, these antibodies seek to bring the two cells close to one another, stimulating the T cell to attack the cancer cell. At least 12 such T-cell engagers have been approved for treating cancers, including leukaemia and myeloma.

Detox effort

But there is still room for improvement, says Carter. Scientists’ growing understanding of tumour proteins and cell types is allowing them to design bispecific and multispecific antibodies that better stimulate an immune response to cancer than do earlier versions and to create a ‘switch’ that prevents the therapy from acting until it is in the right place.

“We’re getting to this point where we’re starting to understand biology at a completely different level,” Chen says. “For the field of multispecifics, it really comes down to being able to understand biological complexity well enough to engineer them.”

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