Mice with pancreatic tumours given a novel combination treatment lived 25% longer than those given just high intensity, focused ultrasound (HIFU), and 35% longer than those only given immune checkpoint inhibitors (ICIs). They also lived 40% longer than those not treated at all, according to a study in the Journal of the Royal Society Interface.
A team from the Institute of Cancer Research in London combined the two treatments, already used in hospitals, in their studies and tested them on mice, reports The Independent. The development of a two-in-one treatment for pancreatic cancer could significantly improve survival rates, which have barely improved in the past half a century, say experts.
One is immunotherapy, involving a drug that blocks the protein that stops the immune system from attacking cancer cells, and which has had major success against some types of cancer. But pancreatic cancer tumours have a thick outer layer that stops the drug from breaking through the barrier.
The second treatment involves high intensity, focused ultrasound (HIFU) blasting of the tumour with pulses of sound waves. Small bubbles are then created in the cells, which bounce around vigorously and puncture holes in the protective barrier, enabling the drug to work effectively.
Researcher Dr Petros Mouratidis said that such treatment could add several extra months of life in humans. However, the mice were given only a single treatment, and researchers hope the two-in-one therapy could potentially cure pancreatic cancer if given as an extended course.
Trials could start within two years and, if successful, the treatment could be in widespread use just three years later.
He is also optimistic that the treatment will work late in the disease, which is vital as pancreatic cancer is usually not diagnosed until it has spread around the body. It is difficult to detect early as the organ is buried deep inside the body, so tumours cannot be seen or felt.
Study details
Pulsed focused ultrasound can improve the anti-cancer effects of immune checkpoint inhibitors in murine pancreatic cancer
Petros X. E. Mouratidis, Marcia Costa, Ian Rivens, Elizabeth E. Repasky and Gail ter Haar
Published in Journal of the Royal Society Interface on 7 July 2021
Abstract
Pulsed high-intensity focused ultrasound (pHIFU) uses acoustic pressure to physically disrupt tumours. The aim of this study was to investigate whether pHIFU can be used in combination with immune checkpoint inhibitors (ICIs) to enhance survival of tumour-bearing animals. Murine orthotopic pancreatic KPC tumours were exposed both to a grid of pHIFU lesions (peak negative pressure = 17 MPa, frequency = 1.5 MHz, duty cycle = 1%, 1 pulse s−1, duration = 25 s) and to anti-CTLA-4/anti-PD-1 antibodies. Acoustic cavitation was detected using a weakly focused passive sensor.
Tumour dimensions were measured with B-mode ultrasound before treatment and with callipers post-mortem. Immune cell subtypes were quantified with immunohistochemistry and flow cytometry. pHIFU treatment of pancreatic tumours resulted in detectable acoustic cavitation and increased infiltration of CD8+ T cells in the tumours of pHIFU and pHIFU + ICI-treated subjects compared with sham-exposed subjects. Survival of subjects treated with pHIFU + ICI was extended relative to both control untreated subjects and those treated with either pHIFU or ICI alone.
Subjects treated with pHIFU + ICI had increased levels of CD8+IFNγ+ T cells, increased ratios of CD8+IFNγ+ to CD3+CD4+FoxP3+ and CD11b+Ly6G+ cells, and decreased CD11chigh cells in their tumours compared with controls. These results provide evidence that pHIFU combined with ICI may have potential for use in pancreatic cancer therapy.
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