Treating glioblastoma, the most common type of malignant brain tumour in adults, with a vaccine – this highly intriguing prospect was demonstrated by a recent phase I study published in Nature Cancer, offering encouraging results, both in terms of safety and of potential efficacy. Another innovative aspect of the treatment is the fact that the vaccine created is “tailor-made”, designed based on the genetic traits of each individual patient's cancer.
Glioblastoma is a brain cancer that is especially difficult to treat. It grows quickly, tends to infiltrate surrounding tissues and, in the majority of cases, recurs even after surgery, radiotherapy, and chemotherapy. Average survival rates are, in fact, still low. In recent years, one of the most promising areas of study for the treatment of this disease has been immunotherapy: therapies that help the immune system to recognise and destroy a cancer’s cells. What we have here is another form of immunotherapy, but of an entirely revolutionary sort. When we talk about vaccines, we often think solely about infectious disease prevention, but in this case we are looking at a treatment.
In order to develop it, the researchers analysed the molecular and genetic structures of the tumours of every patient enrolled in the study, so as to identify their “neoantigens”, fragments of altered proteins produced by tumour mutations, which are not found in healthy cells. These represent ideal targets for the immune system. Vaccines were created based on this information, each containing genetic instructions specific to each patient’s individual tumour. The goal was to train T lymphocytes, one of the immune system’s “weapons”, to recognise and selectively attack cancer cells, reducing the risk of harm to healthy tissues.
The phase I study involved nine adults with new glioblastoma diagnoses, for each of whom a personalised vaccine was prepared following surgery and during the course of their radio-chemotherapy treatment programs. The first doses were administered approximately ten weeks after surgery, with scheduled boosters over time. The data showed that the vaccine was generally well tolerated and did not cause any serious side effects. What’s more, it generated a strong and direct immune response against numerous tumour neoantigens in almost all of the patients.
Although the number of patients was small and the study was not designed to prove conclusive clinical efficacy, some participants demonstrated longer than expected recurrence-free survival. In one case in particular, at almost five years from the date of diagnosis there were no signs of cancer recurrence, an exceptional outcome for this disease.
Although the outcomes are entirely preliminary and the number of patients treated is very small, this study confirms the feasibility of producing completely personalised vaccines within a time-frame compatible with patients’ treatment regimens. Furthermore, it shows that the immune system can be taught to recognise numerous specific cancer targets within each individual. According to the authors, this approach could be further enhanced by combining it with other forms of immunotherapy already being used against different types of cancers.
However, phase II and III studies involving larger numbers of patients will be needed to confirm whether these vaccines are truly able to increase survival in comparison to currently available treatments. What is certain is that this study, like many others that employ vaccines therapeutically in the fight against cancer, brings us another step closer to what will be, for many, the future of clinical practice – one where we can create therapies specifically designed to treat each individual patient, “personalised medicines” based on the unique characteristics of each person's disease. If these outcomes are verified, personalised vaccines could be one of the most advanced treatments in the field of oncology in years to come.