Dampening the immune system improves response to mesothelioma treatment

Thursday 24 October 2013

The body's natural defences can sometimes work against cancer treatments

Suppressing the body's natural defences could improve how well mesothelioma patients respond to certain treatments, a US study suggests.

Mesothelioma develops in the thin membranes covering the lungs or abdomen. Though rare, it is the most common form of cancer to affect people exposed to asbestos.

The study used a drug called an immunotoxin - a bacterial toxin linked to an antibody fragment - which recognises a molecule on the outside of tumour cells to selectively target and kill them while leaving normal cells undamaged.

Previous trials of immunotoxins for mesothelioma have not been effective though because patient's produce their own antibodies that attack the immunotoxin and prevent it from reaching the cancer cells.

But now, researchers from the National Cancer Institute in the US have combined an immunotoxin called SS1P with two other drugs - pentostatin and cyclophosphamide - that suppress the body's natural defences and reduce the number of antibodies targeting the therapy.

Dr Raffit Hassan and colleagues treated 10 patients with late-stage disease and the combined treatment successfully reduced the number of antibody-generating immune cells in the patient's blood and increased the amount of SS1P available to target the tumour cells.

Tumours in three of the patients shrank, including two patients who had originally failed to respond to anti-cancer drugs.

These patients showed a substantial improvement following SS1P treatment, according to the study published in Science Translational Medicine.

None of the 10 patients suffered infections as a result of suppressed immunity and the treatment was well tolerated.

Dr Hassan and his team plan to follow these early results with a larger study of the treatment, which could provide an alternative for patients who have not responded to other drugs.

Dr James Spicer, a Cancer Research UK immunotherapy expert, said: "Mesothelioma is notoriously hard to treat, so these impressive early results are encouraging. Linking an antibody fragment to a toxin is a potentially powerful way of delivering drugs to a tumour, but this and some other biological therapies have previously struggled because the patients' own immune system fought back against the drug."

"Controlling this immune response could increase the amount of drug that reaches the tumour. This new approach looks promising, and it will be interesting to see the results of larger trials in the coming years."

No Error

Hassan R, et al. (2013). Major Cancer Regressions in Mesothelioma After Treatment with an Anti-Mesothelin Immunotoxin and Immune Suppression, Science Translational Medicine, 5 (208) 208ra147-208ra147. DOI: 10.1126/scitranslmed.3006941