Diverse Bispecific Strategies Emerging Across GI Cancers
Key Points
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Bispecific T-cell engagers and biparatopic antibodies are novel therapies used for the treatment of gastrointestinal (GI) cancers.
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GI cancer experts discussed the differences between the two during the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.
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Zanidatamab, a biparatopic antibody, has shown durable responses and may help overcome mechanisms of treatment resistance.
Bispecific antibodies have opened up a new way to target and treat GI cancers.
Shruti Patel, MD, of Stanford Medicine, spoke with Udhayvir Singh Grewal, MD, of the University of Iowa Health Care Medical Center, at the 2025 ASCO Annual Meeting about the differences between bispecific T-cell engagers and biparatopic antibodies.
Bispecific T-cell engagers have one epitope that attaches to an antigen expressed on the surface of tumor cells and another epitope that pulls in the host’s T cells to engage a killing action on the cell. They are “extremely potent drugs, but do have some concerning side effects that we have to monitor really closely,” including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, Dr. Patel said.
Comparatively, biparatopic antibodies, such as zanidatamab, essentially attach both epitopes to the same antigen on the tumor cell. The theory is that this different mechanism of action may help to overcome treatment resistance in GI cancers.
“With the duration of response seen with zanidatamab, the hope seems real, and that is moving that part of the field forward,” Dr. Patel said. “We are really hopeful that these bispecifics are going to help us unlock the targeted therapies and move us past chemotherapy.”