Scientists from King's College London have found a way to boost the immune system to help it fight back against cancer.
The breakthrough involves the first ever use of a combination of chemotherapy and a drug being trialled as a treatment for neonatal jaundice, that together help kick start the body's natural defences.
The advance, which is published in the journal Clinical Cancer Research today, involves the targeting of 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.
Scientists have already shown in the laboratory that chemotherapy can trigger immune responses against cancer, but the King's 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 a major breakthrough, researchers found that in preclinical trials, a drug being tested for the treatment of jaundice (SnMP), effectively prevented the suppression of the immune response stimulated by chemotherapy, allowing the immune system to efficiently attack the cancer.
The authors suggest that inhibiting HO-1 with SnMP shares many similarities with 'checkpoint inhibitor' antibody drugs, a new group of therapies, the first of which are now in routine use in cancer clinics around the world.
The report's authors, Dr James Arnold and Professor James Spicer, from King's College London, are working with Cancer Research UK to develop these observations into a first-in-human clinical trial for this combination treatment.
Speaking about the breakthrough Dr Arnold said: "In lab tests SnMP plus chemotherapy combination compared favourably to the current checkpoint inhibitor therapy used in the clinic, suggesting that there could be significant scope for targeting HO-1 in patients.
"The full benefit to patients will be better understood once we move these exciting observations into clinical trials. However, in our preclinical models, when combined with chemotherapy, the efficacy of tumour control was comparable to that of the 'gold-standard' immuno-therapy currently being used in the clinic.
"We are hopeful that our research will represent a new drug class and combination treatment that will help to awaken the immune system to attack cancer."
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Preclinical research work was funded by the European Research Council and Cancer Research UK.
The Heme Oxygenase
The Heme Oxgenase (HO) family of proteins is responsible in healthy tissues for the breakdown of haem, which is released from dying red blood cells. In tumours, HO-1 has long been known as an enzyme that has tumour-promoting properties, but until now the route to exploit these observations to help patients remained elusive. SnMP is a potent HO-1 inhibitor which has been previously given to babies and children with diseases affecting the breakdown of red blood cells, where it targets HO activity in the liver. Chemotherapy is widely administered to patients with cancer and can stimulate the immune system to identify the cancer cells. Dr Arnold's study published in Clinical Cancer Research presents a compelling rationale for repurposing SnMP as a novel immune checkpoint drug in cancer, where it is capable of boosting the weak immune response produced by chemotherapy.
About King's College London
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About Cancer Research UK
- Cancer Research UK is the world's leading cancer charity dedicated to saving lives through research.
- Cancer Research UK's pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives.
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- Cancer Research UK has been at the heart of the progress that has already seen survival in the UK double in the last 40 years.
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