Patients with advanced head and neck cancer face a very complex clinical situation when the disease stops responding to conventional treatments: therapeutic options become very limited. This reality, detected in routine clinical practice, is the starting point for new lines of research promoted by ICO and IDIBELL within the framework of the Bellvitge Comprehensive Cancer Center, where care and research work in an integrated way to respond to unmet medical needs.
In this context, a multidisciplinary team of professionals from the Catalan Institute of Oncology (ICO), the Bellvitge Biomedical Research Institute (IDIBELL) and the Vall d’Hebron University Hospital, with the collaboration of the biotechnology company Theriva™ Biologics, has published in the prestigious journal Clinical Cancer Research the results of a Phase I clinical trial exploring a new therapeutic strategy for recurrent or metastatic squamous cell carcinoma of the head and neck. ICO has been the main sponsor of the clinical trial and the coordinating centre.
In the trial, the team analyzes the combination of the VCN-01 oncolytic virus, developed by Theriva™ Biologics from technology developed in the laboratory of Dr. Ramon Alemany, of the Cancer Immunotherapy group of ICO and IDIBELL, and the immunotherapy drug durvalumab. The first results show that the new strategy is viable and safe under certain conditions, and point to its potential to improve the immune system’s response against the tumour: modifying the tumour microenvironment, which is often hostile to immune action, could make the cancer more treatable.
A virus that ‘modifies’ the tumour to make it more vulnerable
Many advanced tumors develop mechanisms that hinder the action of the immune system and limit the effectiveness of treatments. To overcome this barrier, the researchers have used VCN-01, a virus genetically modified to replicate exclusively inside tumour cells. Once inside the tumour, the virus not only causes the destruction of cancer cells, but also alters the structure of the tumour tissue, and thus facilitates the entry of both drugs – in this case, durvalumab – and immune cells.
The results obtained suggest that this therapeutic combination can effectively contribute to reversing resistance to immunotherapy in some patients. According to Ricard Mesía, head of the Medical Oncology Service at ICO Badalona, a specialist in head and neck cancer and author of the study, “this treatment is not only viable, but also manages to profoundly modify the tumour microenvironment. Analysis of the biopsies shows a significant increase in active immune cells within the tumor.” Mesía stresses that “this change is especially relevant because it could make immunotherapy-resistant tumours sensitive to drugs such as durvalumab again“.
Everything points to a reactivation of the immune response, and biological analyses confirm it: the markers associated with immunosuppression decrease, and the microenvironment becomes more inflamed and accessible to the action of the immune system.
A possible alternative for patients with few therapeutic options
Although this is an initial study with a small cohort – 20 participants – the researchers believe that the results justify the development of new, larger clinical trials. From a clinical point of view, promising signs of antitumour activity were detected, with prolonged survival in some cases – some patients exceeded 17 months of survival – and a significant proportion of patients alive after one year of follow-up – more than 60%-.
In addition, the researchers also highlight that some patients who had stopped responding to immunotherapy showed a new response to subsequent treatments after receiving the combination of VCN-01 and durvalumab, a result that points to a possible reactivation of tumor sensitivity, which is very relevant in this context.
Beyond the concrete results, this work exemplifies the model of the Bellvitge Comprehensive Cancer Center: an environment in which the needs detected at the bedside of the patient guide research, and where research is translated into new strategies that can be returned to clinical practice. This constant connection between care and research allows us to move towards more personalised and effective treatments, especially in tumours with a poor prognosis.
The researchers stress that these results will have to be confirmed in larger, larger and controlled clinical trials, but they point out that the use of oncolytic viruses to modify the tumour microenvironment could open up a new therapeutic avenue for patients with advanced head and neck cancer, one of the areas with the greatest need for innovation in oncology.
About IDIBELL
The Bellvitge Biomedical Research Institute (IDIBELL) is a research centre created in 2004 and specialising in cancer, neuroscience, translational medicine and regenerative medicine. It has a team of more than 1,500 professionals who, from 73 research groups, publish more than 1,400 scientific articles a year. L’IDIBELL is participated by the Bellvitge University Hospital and the Viladecans Hospital of the Catalan Health Institute, the Catalan Institute of Oncology, the University of Barcelona and the City Council of L’Hospitalet de Llobregat.
IDIBELL is a member of the Campus d’Excelencia Internacional of the University of Barcelona HUBc and is part of the CERCA institution of the Generalitat de Catalunya. In 2009 it became one of the first five Spanish research centres accredited as a health research institute by the Carlos III Health Institute. In addition, it is part of the HR Excellence in Research program of the European Union and is a member of EATRIS and REGIC. Since 2018, IDIBELL has been an Accredited Centre of the AECC Scientific Foundation (FCAECC).