Cancer Drug Candidate Induces Dual Response in Preclinical Study
A small molecule, now in clinical trials, increases activity of immune cells and sensitivity of tumors to immune attack.
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Cancer immunotherapy drugs called PD-1 inhibitors are widely used to stimulate the immune system to fight cancer, but many patients either don’t respond or develop resistance to them. A new small-molecule drug candidate being tested in an early-stage clinical trial aims to improve patient responses to immunotherapy.
Now scientists have shown, in a study published today in Nature, that the small molecule works through two different mechanisms to slow tumor growth and increase survival in lab animals.
Researchers from the Tumor Immunotherapy Discovery Engine (TIDE) at the Broad Institute of MIT and Harvard, AbbVie, and Calico Life Sciences report that the molecule simultaneously makes tumors more sensitive to immune attack and boosts the activity of immune cells to fight tumors in mice.
The molecule works by blocking the PTPN2 and PTPN1 proteins, which normally act to shut down the ability of cells to sense signals that activate immune cells. The researchers found that by inhibiting PTPN2/N1, the molecule turns immune cells called T and NK cells into more effective killers of tumor cells and also makes tumor cells more vulnerable to attack. Blocking PTPN2/N1 also helps reduce T-cell exhaustion, a type of T-cell dysfunction that is thought to underlie some cancer immunotherapy resistance.