Scientists at King’s have found a way to boost the immune system to help it fight back against cancer, by using a never before tried combination of chemotherapy and a drug being trialled as a treatment for neonatal jaundice. Together the two treatments help to kick-start the body’s natural defences.

The breakthrough, published in Clinical Cancer Research, involves targeting an enzyme called Heme Oxygenase-1 (HO-1), which is active in a variety of cancers. HO-1 can promote the growth of tumours by preventing the immune system from effectively attacking cancer cells.

It has already been shown that chemotherapy can trigger immune responses against cancer, but the team have found that these responses are suppressed by non-tumour cells called ‘macrophages’, which reside in the tumour and produce the HO-1 enzyme.

In preclinical trials, a drug being tested for the treatment of jaundice (SnMP), effectively prevented the suppression of the immune response stimulated by chemotherapy. This allowed the immune system to efficiently attack the cancer.

 

The authors suggest that inhibiting HO-1 with SnMP shares many similarities with ‘checkpoint inhibitors’, a new group of immunotherapies which help release the brakes on the immune response against the tumour, some of which are currently in clinical use.

Dr Arnold commented: ‘In lab tests the efficacy of SnMP plus chemotherapy as a drug combination compared favourably in our preclinical models to that of the ‘gold-standard’ immune checkpoint inhibitor currently being used in the clinic , suggesting that there could be significant scope for targeting HO-1 in patients. However, the full benefit to patients will be better understood once we move these exciting observations into clinical trials.’

The report’s authors, Dr James Arnold and Professor James Spicer, are working with Cancer Research UK to develop these observations into a first-in-human clinical trial for this combination treatment.

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