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Anti-PD-1 / L1 treatments, which eliminate "checkpoints" that prevent the immune system from fighting cancer, have been hailed as a major breakthrough in treatment. But not all patients respond to checkpoint inhibitors. Researchers are exploring new ways to improve their effectiveness, and a team led by the Cedars-Sinai Medical Center has identified a popular blood-medicine drug Bristol-Myers Squibb as a potential amplifier.
The wizard is Sprycel, an FDA approved drug in 2006 and classified as an essential drug by the World Health Organization. The product generated $ 2 billion in revenue for BMS in 2018 and, most recently, it has expanded the FDA's approval as a front-line treatment for children with some form of leukemia acute lymphoblastic.
When it was administered to mice with an anti-PD-1 drug, Sprycel increased the effectiveness of therapy on several types of tumors, the team said in a study published in the Science Advances review. Scientists from Bristol-Myers and the University of Colorado also participated in the study.
The researchers began their search for an anti-PD-1 booster using a genomic tool for screening tumor cell lines for targets for which there are FDA-approved treatments. They identified the DDR2 gene as the candidate of choice. The gene encodes a tyrosine kinase receptor that helps tumors spread into healthy tissue.
Sprycel works by inhibiting DDR2. The team chose the drug for additional testing "because of its status as the most potent inhibitor of DDR2 in vitro and in vivo and the prevalence of its use in clinical trials on tumors with specific activating mutations." of the DDR2, "the authors said in the same newspaper. study.
When they tested the combination of Sprycel and anti-PD-1, "we found that the number of cures in mice ranged from 10 to 15% to 90% in some cases," said the author. Correspondent of the study, Dan Theodorescu, MD, Ph.D., director of Cedars-Sinai Cancer, in a video interview.
"If our results are confirmed by clinical trials, it means that by combining the two types of drugs, we may be able to better reduce or even eliminate tumors of bladder, breast, and colon cancers. melanoma and sarcoma, "he said.
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Combined approaches to improve immunotherapies have been extensively studied on different types of cancer. According to the authors, more than 1,100 clinical trials were investigating the inhibition of PD-1 in combination with another treatment starting in 2017. While many use targeted therapies like Sprycel, some pursue different tactics.
Researchers at the University of Southampton, for example, have already shown that the combination of varlilumab, the immunotherapy targeting Celldex Therapeutics CD27, with CD27-targeted immunotherapies, led to better results in murine models of Cancer. A team led by scientists at Massachusetts General Hospital recently discovered that adding Amgen Imlygic cancer killer virus to Novartis MEK inhibitor MEK-1 and Mekinist, helped fight tumors in almost all animals during a study on mice with melanoma.
Scientists at Columbia University also found that the combination of checkpoint inhibitors with pentoxifylline, a drug used to improve blood flow, prevented regulatory T cells (Tregs) from suppressing cancer-fighting T cells. And Seres Therapeutics, in collaboration with the MD Anderson Cancer Center and the Parker Institute, is studying the use of the gut microbiome to improve control point responses.
BMS has already begun evaluating its PD-1 inhibitor, Opdivo, with Sprycel in non-small cell lung cancer. The Phase 2 study should be read in April 2021.
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