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15 juli 2019: Bron: Clinical Cancer Research (met dank aan Vincent die mij hierop wees)

Wanneer blaaskankerpatienten een week vooraf aan een operatie een vorm van immuuntherapie krijgen met een gemoduleerd verkoudheidsvirus ( Coxsackievirus A21) dan blijkt deze vorm van immuuntherapie al substantieel veel kankercellen te hebben gedood omdat het verkoudheidsvirus een immuunreactie oproept. Bij 1 patient was zelfs alle kanker al verdwenen in 1 week tijd.

Slechts 15 patienten deden mee aan deze fase I studie maar allen profiteerden. De onderzoekers stellen dan ook dat dit wel eens een verandering kan bewerkstelligen in de aanpak van blaaskanker.  Ook omdat deze aanpak geen bijwerkingen geeft.

Prof Pandha said:

"Reduction of tumour burden and increased cancer cell death was observed in all patients, and removed all trace of the disease in one patient following just one week of treatment, showing its potential effectiveness," he said.

"Notably, no significant side effects were observed in any patient." 

Op de website van de BBC legt prof. dr. Pandha het nog maar eens uit in 1 zin hoe immuuntherapie met een gemoduleerd virus werkt:

"The virus gets inside cancer cells and kills them by triggering an immune protein - and that leads to signalling of other immune cells to come and join the party," prof. dr. Pandha said.

In Science Daily wordt deze studie uitgebreid besproken: 

Strain of common cold virus could revolutionize treatment of bladder cancer.

Het orginele abstract van deze studie: 

Viral targeting of non-muscle invasive bladder cancer and priming of anti-tumour immunity following intravesical Coxsackievirus A21 staat hieronder. Voor het volledige studierapport moet worden betaald.

Viral targeting of non-muscle invasive bladder cancer and priming of anti-tumour immunity following intravesical Coxsackievirus A21

Nicola E Annels, David Mansfield, Mehreen Arif, Carmen Ballesteros-Merino, Guy R Simpson, Mick Denyer, Sarbjinder S Sandhu, Alan Melcher, Kevin J Harrington, BronwYn Davies, Gough Au, Mark Grose, Izhar N Bagwan, Bernard A. Fox, Richard G Vile, Hugh Mostafid, Darren Shafren and Hardev Pandha
Carmen Ballesteros-Merino
Earle A. Chiles Research Institute, Providence Portland Medical Center
Guy R Simpson
Clinical and Experimental Medicine, University of Surrey
Mick Denyer
Oncology, Leggett Building, University of Surrey
Sarbjinder S Sandhu
Urology, Kingston Hospital NHS Foundation Trust
Alan Melcher
Division of Radiotherapy and Imaging, Institute of Cancer Research
Bernard A. Fox
Robert W. Franz Cancer Center, Earle A Chiles Research Institute
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Abstract

Purpose: The CANON (CAVATAK in NON-muscle invasive bladder cancer) study evaluated a novel ICAM-1-targeted immunotherapeutic-coxsackievirus A21 as a novel oncolytic agent against bladder cancer. Experimental Design: Fifteen patients enrolled on this 'window of opportunity' phase 1 study, exposing primary bladder cancers to CAVATAK prior to surgery. The first nine patients received intravesical administration of monotherapy CAVATAK; in the second stage, six patients received CAVATAK with a sub-therapeutic dose of mitomycinC, known to enhance expression of ICAM-1 on bladder cancer cells. The primary endpoint was to determine patient safety and maximum tolerated dose. Secondary endpoints were evidence of viral replication, induction of inflammatory cytokines, anti-tumour activity and viral-induced changes in resected tissue. Results: Clinical activity of CAVATAK was demonstrated by induction of tumour inflammation and haemorrhage following either single or multiple administrations of CAVATAK in multiple patients, and a complete resolution of tumour in one patient. Whether used alone or in combination with mitomycinC, CAVATAK caused marked inflammatory changes within NMIBC tissue biopsies by up-regulating interferon-inducible genes including both immune checkpoint-inhibitory genes (PD-L1 and LAG3) and Th1-associated chemokines as well as induction of the innate activator RIG-I, compared to bladder cancer tissue from untreated patients. No significant toxicities were reported in any patient, from either virus or combination therapy. Conclusions: The acceptable safety profile of CAVATAK, proof of viral targeting, replication and tumour cell death together with the virus-mediated increases in "immunological heat" within the tumour microenvironment all indicate that CAVATAK may be potentially considered as a novel therapeutic for NMIBC.

  • Received December 17, 2018.
  • Revision received March 6, 2019.
  • Accepted June 27, 2019.

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