Leukemia drug found to stimulate immunity against many cancer types

June 17, 2014

A UCL research mouse (credit: David Bishop, UCL)

A class of drug called p110δ inhibitors, currently being used to treat leukemia, has the unexpected side-effect of boosting immune responses against many different cancers, reports a new study led by scientists at UCL (University College London) and the Babraham Institute, Cambridge.

The drugs have shown such remarkable efficacy against certain leukemias in recent clinical trials that patients on the placebo were switched to the real drug. Until now, however, they have not been tested in other types of cancer.

The new study, published in Nature, provides the first evidence that such drugs can significantly restrict tumor growth and spread and reduce the chances of relapse for a broad range of cancers. The researchers, together with scientists from Genentech, showed that inhibition of the p110δ enzyme helps to boost the body’s immune system to kill tumor cells.

The team showed that inhibiting p110δ in mice significantly increased cancer survival rates across a broad range of tumor types, both solid and hematological cancers. For example, mice in which p110δ was blocked survived breast cancer for almost twice as long as mice with active p110δ. Their cancers also spread significantly less, with far fewer and smaller tumors developing. Survival after surgical removal of primary breast cancer tumors was also vastly improved, which has important clinical implications for stopping breast cancer from returning following surgery. The team’s data further show that following p110δ inhibition, the immune system could develop an effective memory response to completely fight off the cancer.

The p110δ enzyme is a member of the PI3-kinase family, and is sometimes called PI3Kδ. p110δ and the other PI3Ks are hot drug targets for the pharmaceutical industry as they are implicated in many cancers and are readily druggable.

Professor Nic Jones, Cancer Research UK’s chief scientist and director of the Manchester Cancer Research Centre, said: “Treatments that train the immune system to recognize and kill cancer cells are showing huge promise in several types of cancer. This new finding, although only at an early stage, offers the potential to develop more treatments that can do this in many more cancers, including ones that have real need for more effective treatments such as pancreatic cancer.

“If the findings hold true in cancer patients this could make a big difference to many of them. The good news is that because the drugs used in this study are already being used in the clinic, we could see rapid translation of this research into patient benefit.”

“Gilead has a clinical p110delta  inhibitor that is likely to be FDA-approved for use in CLL in the next year, if not earlier,” study co-leader Professor Bart Vanhaesebroeck of the UCL Cancer Institute told KurzweilAI in an email. “This therapeutic approach of stimulation of the anti-tumour immune response by p110delta inhibition in solid tumors could therefore soon be tested in the clinic.

“Other Pharma also have p110delta inhibitors that have been developed for immune-related (non-cancer) disease, such as arthritis and allergy. One could envisage that such drugs could also be used in cancer therapy, based on our findings.  We are also working on a clinical programme of testing p110delta inhibitors in solid tumours, we hope to start these studies within a year, pending approval.

The research was funded by Cancer Research UK, the Biotechnology and Biological Sciences Research Council and the Wellcome Trust.

Abstract of Nature paper

Inhibitors against the p110δ isoform of phosphoinositide-3-OH kinase (PI(3)K) have shown remarkable therapeutic efficacy in some human leukaemias. As p110δ is primarily expressed in leukocytes, drugs against p110δ have not been considered for the treatment of solid tumours. Here we report that p110δ inactivation in mice protects against a broad range of cancers, including non-haematological solid tumours. We demonstrate that p110δ inactivation in regulatory T cells unleashes CD8+ cytotoxic T cells and induces tumour regression. Thus, p110δ inhibitors can break tumour-induced immune tolerance and should be considered for wider use in oncology.