Experimental combinatorial therapy eliminates an incurable brain tumor

A study recently accepted for publication in The Journal of Clinical Investigation describes a new and effective therapy to treat glioblastoma: the concomitant use of ADI-PEG20 together with focal brain radiotherapy. This double treatment completely eliminated the tumour in the animal models used in the study. This study was carried out by researchers from the Institute of Biomedicine of Seville: Dr. Manuel Sarmiento Soto, Dr. Juan García Revilla, and Dr. José Luis Venero, in collaboration with Dr. Nabil Hajji and Dr. Nel Syed of Imperial College London.

Currently, glioblastoma is a terminal disease whose average life expectancy is less than 2 years. The treatments used at present are based on therapies that are more than 30 years old as no significant advances have been made to efficiently combat this type of tumour.

The results of this study offer a new therapeutic option against glioblastoma: the use of the drug ADI-PEG20, which eliminates systemic arginine, in combination with the application of focal brain radiotherapy. With this, it was possible to observe how a brain tumour, incurable to date, was completely eliminated in in vivo models that died of natural causes without showing any manifestation of the disease.

"With this new treatment, we were able to cure animals of an aggressive and terminal disease," says Dr. Sarmiento, "the post-mortem analyses detected how the cerebral immune response, and fundamentally the microglia cells, were activated during the treatment, directing their attack against the tumour cells and thus facilitating the tumour's complete elimination".

The data obtained are a ray of hope for the treatment of patients with this type of tumour, since, regardless of the success of the new anticancer drugs, their efficacy in the central nervous system is currently very limited, largely due to their difficulty in reaching the cancer cells located inside the brain.

Worth noting is another clinical trial (NCT04587830) also focused on another specific type of glioblastoma patient, studying the use of the same drug and whose results are proving to be very promising. Importantly, the drug did not manifest side effects in the patients involved in said trial.

This work has been funded both by Projects of the Ministry of Science and Innovation (RTI2018-098645-B-I00) and the Ministry of Economy and Knowledge of the Andalusia Regional Government (P18-RT-1372), as well as by the Brain Tumor Research, a UK charity focused on finding a cure for all types of brain tumours.

The research team firmly hopes to begin recruiting the first patients for the start of the Phase I clinical trial in the coming months.

About IBiS

The Institute of Biomedicine of Seville (IBiS) is a multidisciplinary centre whose objective is to carry out fundamental research on the causes and mechanisms of the most prevalent pathologies in the population and the development of new diagnostic and treatment methods for them.

The IBiS is made up of 42 consolidated groups and 42 affiliated groups led by researchers from the University of Seville, the Higher Council for Scientific Research (CSIC) and the Virgen del Rocío, Virgen Macarena and Virgen de Valme University Hospitals organised around five thematic areas: Infectious and Immune System Diseases, Neurosciences, Onco-hematology and Genetics, Cardiovascular Pathology, Respiratory / Other Systemic Pathologies and Liver, Digestive and Inflammatory Diseases.

The IBiS depends institutionally on the Department of Health and Families of the Andalusian Regional Government; the Andalusian Health Service (SAS); the Ministry of Economic Transformation, Industry, Knowledge and Universities; the University of Seville and the Higher Council for Scientific Research (CSIC).