Researchers from the University of Rhode Island and Yale University have demonstrated a promising new approach to delivering immunotherapy agents to fight cancer.
The approach involves tethering an immunotherapy agent called a STING agonist to an acid-seeking molecule called pHLIP® (pH-low insertion peptide). The pHLIP molecules target the high acidity of cancerous tumors, delivering their immunotherapy cargo directly to cells in the tumor microenvironment. Once delivered, the STING agonists engage the body’s innate immune response to fight the tumor.
In a study published in Frontiers of Oncology, the team showed that just a single dose of the pHLIP-STING agonist combination eradicated colorectal tumors—even large, advanced tumors—in mice. The treated mice also developed lasting immunity, enabling their immune systems to recognize and fight cancer long after the initial tumors were gone. While the researchers caution that results in mice don’t always translate to humans, the findings do lay the groundwork for a potential clinical trial testing the safety and effectiveness in cancer patients.
“STING agonists are an important class of immuno-modulators, but research has clearly shown that they often don’t work on their own and need to be targeted in some way,” said Yana Reshetnyak, a physics professor at URI and a senior author of the new research. “What we show here is that using pHLIP to target tumors through their acidity, we can successfully go after a variety of different cell types within the tumor microenvironment and achieve synergistic and quite dramatic therapeutic effects.”
Immunotherapy is an emerging approach to fighting cancer. For cancer to survive and spread, tumors need to hide from the immune system. In some cases, they do this by expressing proteins that act as immune cloaking devices—tricking the immune system into thinking tumor cells are normal, native cells. Immunotherapy aims to disable these cloaking devices.
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