Cancer Discov: New drug mix helps overcome resistance to PD-1 immunotherapy

June 1, 2020 /
PRNewswire
BIOON///BIOON -- A new study from researchers at ucla's Jonsson Center for Integrated Cancer explains how genetic disturbances can lead totumorsresistance to immunotherapy -- PD-1 inhibitor resistance and how a new combination of drugs can help overcome resistance to anti-PD-1 therapyteam found that changing the tumor microenvironment with a toll-like receptor 9 agonist ( a nucleic acid sequence that mimicsbacteriainfection) and another immunotherapy drug, NKTR-214 , which stimulates the immune response of natural killer cells , can help induce a strong immune response , making the immune system more effective against attackingtumorWhen these drugs are used in combination with PD-1 blockers, they are able to overcome gene-induced immunotherapy resistance in preclinical modelsimage source: https://cn.bing.com
the development of immunotherapy, such as PD-1 blocking, has changed the outlook for cancer treatmentIt works very well for a significant number of patients, even those with fatalDespite its success in treating deadly cancers, many people do not benefit from treatment or end up experiencing a recurrence of the cancerResearchers are currently studying various combinations of PD-1 blockers and other therapeutic drugs, but there is no easy way to determine which therapeutic drugs are most effective in improving the immune response to potential mechanisms involving resistance to PD-1 blockersResearchers at the University of California, Los Angeles, have been looking for ways to better understand the biology of drug resistance mechanisms in order to develop reasonably advanced combination therapies to overcome themUsing CRISPR/Cas9 genome editing,team createdgeneticdrug-resistant models of JAK1, JAK2 and B2M mutations by knocking out genes in human and mouse cell linesThey studied the mechanisms of interferon-gamma signaling in human melanoma cell lines and mouse cancer models, whichtumorsresistant to PD-1 therapyBased on molecular understanding of these pathways, the team tested strategies to overcome drug resistance in two anti-PD-1 immunotherapy mouse modelsThey conducted a well-designed combination therapy in mice to describe the best choice for combination therapy based on these acquired drug resistance mechanismsclear how to improve the immune response of immunotherapy drug resistance-related mechanisms, it is possible to improve the anti-tumor activity of tumor immunotherapy, and provide more treatment for more patients with difficult treatmentThe combination of PD-1 blockers and NKTR-214 or toll-like receptor 9 agonists found in this study is currently being evaluated in humanclinical trials in patients whotumorsnon-responsive to PD-1 therapythe study was published in the Journal of the American Association for Cancer Research, Cancer Discovery(Bio ValleyBioon.com) Reference: New Drug Scouse help fusion resistance to immunotherapy
Davis Y Torrejon et al.
Overcoming genetically-based-based resistance mechanisms to PD-1 blockade.
Cancer Discovery (2020) DOI: 10.1158/2159-8290.CD-19-1409