Researchers have presented preclinical data on the use of antibody-directed microbubbles to get cytotoxic payloads to tumors. The payload remains encapsulated until an ultrasound pulse bursts the bubbles and triggers the release of the therapeutic.
In a paper published in the journal Theranostics, scientists at research centers in the U.K. describe the creation of VEGFR2-targeted microbubbles. Using a light-emitting compound, the researchers showed tumor bioluminescence was significantly higher in mice that received VEGFR2-targeted microbubbles than in the control group, pointing to the potential to use the platform to minimize the exposure of healthy tissues to cytotoxic drugs.
Antibody-drug conjugates (ADCs) already provide such targeting. One of the payloads explored in the Theranostics paper, SN38, is used in ADCs, most notably in the anti-TROP-2 drug Trodelvy that Gilead Sciences acquired in its $21 billion takeover of Immunomedics.
Like the microbubble approach, ADCs attach a cytotoxic payload to a targeting antibody to deliver the drug to cells that express a particular receptor. By choosing a receptor that is overexpressed on cancer cells, researchers can deliver higher levels of a cytotoxic drug than would be tolerable if given systemically without a targeting mechanism, thereby boosting efficacy and reducing toxicity.
The microbubble approach adds a twist to the idea by encapsulating the payload, potentially further limiting the harm caused to healthy tissues. The payload is only released upon contact with a pulse of ultrasound.
“We not only show the very precise and targeted way microbubbles can be guided to cancer sites but that the efficacy of drug delivery is substantially improved, opening the way to use highly toxic drugs to fight cancer, without the harmful side effects,” Stephen Evans, Ph.D., a University of Leeds professor and co-author of the paper, said in a statement.
The researchers plan to assess the application of the technology to the treatment of advanced colorectal cancer. Other applications discussed in the paper include the treatment of hepatocellular carcinoma and in seniors, some of whom may benefit from repeated low doses of cytotoxic drugs.