Acid discovery raises hopes of improved immunotherapies

Testing acidity in the lab

The acidity of tumours impairs the effectiveness of anti-cancer therapies, according to a new study that could lead to a new generation of immunotherapy treatments. 

Tumours have a more acidic environment (pH 6.5) than normal, healthy tissues (pH 7.2). New research has shown for the first time that this acidity blocks the activities of cytokines. These are proteins critical for mounting potent anti-tumour responses and are used in immunotherapy to activate or enhance the body’s response. 

Furthermore, the researchers have used protein engineering to design new cytokines that can withstand the acidity found in the tumour environment, leading to more effective anti-tumour responses. 

The research was led by Dr Ignacio Moraga, from Dundee’s School of Life Sciences, alongside colleagues from Lille University and the University of Cambridge 

Dr Moraga said, “High doses of a type of cytokine called IL-2 are used in the clinic to treat cancer and our discovery helps explain why this treatment does not work for most people. IL-2 is a very potent cytokine for driving activation of T cells, which are critical to clear tumours, but it is also very sensitive to the acidic environment.” 

Dr Moraga says he and his colleagues are looking forward to furthering the development of these new pH-selective cytokines and expect to enter the first clinical trials within a few years. 

He added: “Having manipulated the sensitivity of IL-2 to boost antitumor responses and decrease toxicity, the aim is to be able to use this mutant to treat human patients with different type of cancers. We are hoping that we will be able to massively improve current therapies and save lives.” 

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