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WashU Team Uses In‑Body Click Chemistry to Assemble Dual‑Target Cancer Drugs

Mouse tests show higher tumor drug buildup with restored activity, prompting preclinical optimization of safety and dosing for possible clinical testing.

Overview

  • The Nature paper, published July 15, reports that Washington University researchers used rapid trans‑cyclooctene–tetrazine click chemistry to join separately given antibodies and antibody‑drug conjugates inside mice.
  • In mouse models of pancreatic, gastric and breast cancer the clicked assemblies accumulated up to 3.2 times more in tumors than standard ADCs and improved survival in treated animals.
  • The method works by causing two antibody components to 'click' together on tumor cells, which drives antibody clustering, increases internalization, and delivers more cytotoxic payload into cancer cells.
  • The team built the system from existing FDA‑approved antibodies, for example EGFR‑targeting panitumumab and HER2‑directed T‑DXd, so the platform can be retargeted without creating wholly new drugs.
  • Researchers report they have reduced off‑target liver uptake through formulation changes and are carrying out further safety, dosing and target‑expansion studies before any clinical trials.