Modified protein provides new route for cancer immunotherapy

An international team of researchers have modified a common protein produced by the immune system making it more tolerant of the acidic environment created by tumours – a potential breakthrough in developing more effective immunotherapy.

The protein, a cytokine known as IL-2, regulates the immune system and helps CD8 T cells and natural killer (NK) cells to attack cancer cells.

The variant created by the research team enables the modified IL-2 protein to work effectively in the hostile acidic environment produced by tumours.

When the modified protein was given as immunotherapy to mice with melanoma the immune system was activated to attack the tumour.

Although the research has currently been undertaken in mice, these promising results, published in Science Immunology, indicate that the same technique could be developed for use in people.

“By exploiting directed evolution, we improved the tissue-specific activity, efficacy and systemic toxicity profile of IL-2, defining Switch-2 as a potential new immunotherapy for cancer, alone or in combination with checkpoint blockade or adoptive cell therapy,” said one of the lead authors, Dr Rahul Roychoudhuri, who is a member of our Cancer Immunology Programme.

The team also note that since IL-2 is not the only molecule responsive to the acidity of the tumour environment, the same techniques could potentially be used to support the development of acid-tolerant variants of other molecules used in cancer treatments.

Gaggero, S. et al IL-2 is inactivated by the acidic pH environment of tumors enabling engineering of a pH-selective mutein Science Immunology

2 Dec 2022