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April 29th, 2021 - Press notes

The future of immunotherapy at the Optimizing Immunotherapy Congress

The benchmark meeting in the field of immunotherapy cancer treatment was held once again, on April 9, in a hybrid format. This year, the presentations focused on the research and development of this type of treatment for various types of tumours, as well as molecular diagnostics.

Understanding which factors make immunotherapy work in some cancer patients and not in others, the structure and genetics of tumours to help select the most appropriate treatment, is the current focus of research in this field. This was evident at the new edition of the Optimizing Immunotherapy, New Approaches, Biomarkers, Sequences and Combinations congress, held on 9 April in a hybrid format and organised by the Hospital del Mar Medical Research Institute (IMIM) and Hospital del Mar. The meeting brought together around twenty of the world's leading experts in research and clinical application of immunotherapy treatments to analyse the latest breakthroughs and the future of immunotherapy. It was backed by the SEOM, SOGUC and CIBERONC.

As the director of the congress, Dr. Joaquim Bellmunt, an IMIM researcher and associate professor at Harvard Medical School, pointed out, "The key point is developing biomarkers and predictive factors of response to the drugs that immunotherapy offers us."  In other words, locating specific targets at which to direct treatment. Achieving this will improve the prognosis and the range of therapy options, and the most appropriate treatment can be chosen through a better understanding of certain mutations in tumour cells and the functioning of immune system cells. This is the crux of the matter: it is no good giving certain treatments to people who will not benefit from them, and it is crucial that patients who they will help actually do receive them", explained Dr. Edurne Arriola, co-director of the meeting, head of the lung cancer section in the Medical Oncology Service at Hospital del Mar and an IMIM researcher.

The challenges of immunotherapy

The greatest challenge in cancer medicine is overcoming tumour cell treatment resistance. Even immunotherapy does not deliver this. "So far, resistance has appeared in a minority of cases, at least in cases of melanoma, and the vast majority of patients who respond to immunotherapy do so in the long term. The study of acquired resistance is key because it allows us to figure out how to prevent it or if there is new vulnerability that allows us to think about how to treat it", explained Dr Antoni Ribas, director of the tumour immunology programme at the Jonsson Comprehensive Cancer Centre and the Parker Institute for Cancer Immunotherapy at the University of California-Los Angeles (UCLA).

In the scope of the latest advances in the clinical application of these treatments, Dr. Ernest Nadal, from the Catalan Institute of Oncology and an IDIBELL and UB researcher, presented the good results of anti-PD-L1 immunotherapy in the control of small cell lung cancer, a very aggressive type of tumour with few treatment options. Dr. Mafalda Oliveira, a breast cancer specialist at Vall d'Hebron University Hospital and a VHIO researcher, said that in the case of HER2-positive breast cancer, "Research has led the way to treatments aimed at eliminating tumour cells that have a certain biological characteristic, such as HER2 protein positivity. Although not all patients benefit from this drug, we see that the benefit is extraordinary. One of the key building blocks for precision medicine that seeks to attack specific targets and improve the outcomes of immunotherapy is to develop biomarkers that predict which patients may benefit."

In liver cancer, current immunotherapy treatments can improve patient survival by more than six months compared to standard approaches to viral tumours. "In the short term, the use of immunotherapy in patients with non-viral liver cancer should be considered with more caution and approved therapeutic alternatives should be evaluated", explained Dr. Josep Maria Llovet, director of the liver cancer programme at Mount Sinai in New York and a researcher at IDIBAPS-Hospital Clínic. Nevertheless, he also pointed out that "We need to look for new combinations of immunotherapy to offer an alternative."

Dr. Begoña Pérez, from Virgen del Rocío University Hospital in Seville, explained that this approach "is a new option for initially treating patients with metastatic urothelial cancer. This type of therapy is producing positive results for the first time as a front-line treatment." Along the same lines, Dr. Mariano Provencio, from the Spanish Lung Cancer Group and a doctor at Puerta de Hierro University Hospital in Madrid, said that "We are talking about making potentially and mostly lethal tumours curable, paving the way for a change in the therapeutic approach at a global level, which would increase the number of patients who can finally be cured."

The importance of biomarkers

"Identifying biomarkers (which allow us to detect a disease or make a prognosis) is one of the great oncology revolutions from the past few years and, thanks to research, we are identifying more every day", explained Dr. Joan Albanell, head of the Medical Oncology Service at Hospital del Mar and head of the IMIM Oncology Research Programme, who moderated the round table on this field. "Being able to connect and compare thousands and, very soon, millions of genomes is what will drive the medical discoveries of the next decade", he said. 

Biomarkers in breast cancer were the focus of the presentation by Dr. Mar Albà, from the Biomedical Informatics Research Programme (GRIB) of the IMIM and UPF, in which she highlighted the growing use of tools for analysing the genome of tumours in order to locate the most appropriate therapeutic targets. In this field, "The study of messenger RNA (the molecule that allows DNA to manufacture proteins) leads us to new treatment options. However, the analysis of the transcriptome (the set of messenger RNAs in a cell), although applied in research, is not common in the approach to patients in hospitals."

Similarly, David Casadevall, from Savana Médica, explained how artificial intelligence and data analysis help to predict the efficacy of immunotherapy-based cancer treatments and any possible adverse effects, making it possible to select the most appropriate alternative. Dr Pedro Simões da Rocha discussed how characterising the tumour microenvironment reveals different immunological phenotypes, useful observations for generating different predictive biomarkers and creating new and promising expectations for cancer cures. Meanwhile, Memorial Sloan Kettering Cancer Centre researcher , Dr Guillem Argilés, discussed the relationship between the human microbiome and immunotherapy, identifying it as a possible biomarker. "An important and clinically relevant aspect is whether manipulating the gut microbiome could make immunotherapy-unresponsive patients actually respond to the treatment", he said.

Dana-Farber Cancer Institute researcher, Meredith Regan, discussed how understanding treatment-free survival in cancer could be an endpoint for clinical research and could help characterise the effects of treatment. Thomas Powles, director of the Barts Cancer Centre in the UK, focused on the usefulness of the liquid biopsy technique in muscle-invasive bladder cancer in determining prognosis. In the cases analysed, patients who tested positive had a significantly higher risk of relapse. On the other hand, Dr. Manel Esteller, director of the Josep Carreras Leukaemia Research Institute, discussed the role of epigenetics (variations in gene functions) in predicting the benefit of immunotherapy. His study leads the way to improved treatments. "The microenvironment surrounding the tumour is crucial for understanding the response to immunotherapy", he said.

Towards personalised medicine

The last round table of the congress, moderated by Dr. Joaquín Arribas, the director of the IMIM, analysed the future of immunotherapy. In this sense, he highlighted the possibility of initiating the immune system's response with therapeutic vaccines, which attack the tumour once it has appeared. In a similar vein, Dr. Leticia de Mattos, from IrsiCaixa at Germans Trias i Pujol University Hospital, presented work on the development of a vaccine of this type based on neoantigens (abnormal proteins in tumour cells that send a warning if these are cancerous and need to be destroyed). And Dr. Alena Gros, from VHIO, explained a different approach, involving the use of tumour-infiltrating lymphocytes. In this case, those that recognise the tumour are selected, amplified, activated and injected back into the patient. "This treatment offers an alternative to patients who have none, personalised therapy, which must be tailor-made for each patient and is not yet ready to be applied on a large scale", she warned.

Dr. Anna Bigas, IMIM researcher and scientific director of CIBERONC, explained the latest advances in CAR-T cell therapies, based on cells from the patient's own immune system that are genetically modified to fight cancer. She said that, at present, "We are close to achieving a new generation of cellular immunotherapy using allogeneic (donor) CAR-T cells, based on NK cells (natural killer lymphocytes) and combinations with monoclonal antibodies and enzyme enhancers that will pave the way to the treatment of many more types of tumours and other diseases."

Finally, Dr. Antonio Calles, from Hospital General Universitario Gregorio Marañón, reviewed the most current studies combining immunotherapy with other treatments, which have proven to be more effective for more patients and more types of tumours. And Dr. Pedro Berraondo, from the CIMA University of Navarra, discussed the latest advances in combining one or more immuno-oncology treatments, with results that improve response and avoid adverse effects.