L’immunothérapie - qui consiste à exploiter le système immunitaire des patients à des fins thérapeutiques - connaît des avancées singulières depuis plusieurs années. Cependant, un nombre encore trop important de patients ne répond pas à ces traitements, poussant les chercheurs et cliniciens à constamment explorer de nouvelles approches.
Dans cet article, nous proposons une approche innovante qui combine différents traitements existants. Le système immunitaire des patients a la capacité reconnaitre et d’éliminer les tumeurs avec la même efficacité qu’il protège contre des infections virales ou bactériennes. Cependant, le fort potentiel du système immunitaire est inhibé par différents mécanismes déployés par les tumeurs.
Ici, nous proposons un nouvel axe de traitement en deux phases. Lors de la première étape, nous proposons d’initier des réponses immunitaires contre les tumeurs. Appelée priming, cette étape vise à induire et stimuler des réponses immunitaires spécifiquement dirigées contre les tumeurs. Alors que cette étape de priming peut se faire avec les traitements conventionnels tels que la chimiothérapie et la radiothérapie, il y a fort à penser que la vaccination serait une approche particulièrement efficace pour initier des réponses immunitaires contre les tumeurs. Une fois les réponses immunitaires activées, alors la seconde étape, dite boost, consiste à prélever sélectivement les cellules immunitaires des patients ayant une activité anti-tumorale, à les multiplier en laboratoire puis à les réinjecter aux patients, un procédé appelé thérapie cellulaire. L’hypothèse sous-jacente à ce concept est que cette armée de cellules activées et éduquées à trouver et détruire les tumeurs serait moins abondante et moins efficace s’il n’y avait pas eu de priming préalable.
Un avantage important à ce concept est que tant la vaccination que la thérapie cellulaire (ainsi que la chimiothérapie et la radiothérapie) sont des traitements déjà en cours en clinique, offrant la perspective de pouvoir rapidement tester le concept du prime/boost chez les patients et d’en voir les bénéfices.
Lire la publication en ligne sur le site de Nature rédigée par Alexandre Harari , Michele Graciotti, Michal Bassani-Sternberg et Lana E. Kandalaft.
This paper discusses how to boost further current immunotherapy approaches, how best to match a specific immunotherapy to each patient and tumor’s characteristics and how novel technological advances can be used in the clinic to increase therapeutic benefits.
In particular, this study proposes a novel coupled approach in which an initial therapy aims to trigger a spontaneous immune response against tumors in the patient. This initial step, called “priming”, can be carried out with several treatments, from standard chemotherapy, to radiation or patient vaccination. This priming therapy should be carefully selected and adapt to each patient and tumor’s features in order to achieve the best results. After priming, a careful analysis with state-of-the-art technologies of the activated immune responses is aimed at selecting the immune cells most active against the tumor. These cells are then taken from the patient, cultured and potentiated in the laboratories and re-injected into the patient as a second treatment called “boost”. The major novelty in this proposed prime & boost approach is the fact that it combines different treatments that have so far been tested mostly alone, aiming to produce even stronger effects once coupled.
One of the major advantages in activating the immune system to fight tumors is in the so-called immunological memory: the ability of the immune system to quickly and specifically recognize a pathogen that the body has previously encountered and initiate a corresponding immune response. This effect is particularly important in cases when the disease strikes back after an initial global remission, which unfortunately are quite common. I’m convinced that if we are efficient in instructing the immune system to recognize and combat the cancer, our patients will always be equipped with powerful inner “weapons” against this disease, an aspect that is not guaranteed with other more “canonical” and standard treatments. This is what we, as cancer immunologists, are mainly trying toachieve, exploring different avenues to build a powerful, spontaneous and inner response against cancer.
In particular, among the different immunotherapies now available, I decided to focus on cancer vaccines. This strategy consists in using a specific type of immune cells called dendritic cells whose role is to recognize pathogens present in the human body and send a type of “alarm signal” to the rest of the immune system to fight it. Consequently, these type of cells play a crucial role in cancer immunotherapy and I believe that manipulating them and improving their cancer recognition abilities constitute an invaluable therapeutic opportunity.
My last publication fits in the cancer immunology field at large. In it, my co-authors and I propose a novel approach named “prime & boost” that builds on previous evidence and therapies to activate an even more powerful immunological response in cancer patients. In particular, we propose to combine cancer treatments that so far have been used mostly alone, with the main aim to build a powerful and enduring immunological response in cancer patients. Within this approach, especially for the priming phase, we included also standard treatments (such as chemotherapy or radiation) that have recently been shown to stimulate initial immune responses. This aspect can contribute to create a bridge with the rest of the cancer research community, in an effort to work together, merge competences and carefully combine precious knowledge in the fight against such a complex disease.
The novel approach we proposed aims not only to advance the cancer immunology field and our current knowledge, but also importantly to contribute to increase therapeutic benefits for cancer patients. By combining different treatments currently available to treat patients, based on their role in either starting an immune response (priming phase treatments), or potentiating an already existing one (boosting treatments), our approach can potentially improve disease control or its complete disappearance and ultimately the life expectancy of cancer patients. In addition to this, given the sheer number of different treatments currently available for the priming phase, in the same study guidelines, we propose how best to match a priming treatment with the patient’s characteristics, in order to achieve the best results.
The next step will be to test this approach in patients in a clinical trial, in hospital settings. Luckily, the therapies involved in both the priming and the boosting steps have already entered the clinic and been approved for clinical use. Thus, protocols and procedures are already available to combine therapies for a priming effect with a subsequent boosting step, as we propose, and finally assess therapeutic outcomes, directly at the patient level. If successful, this approach will importantly contribute to the general advancement of cancer immunology and improve therapeutic benefits and the quality of life for cancer patients.