The promises of immunotherapy
Honored by the 2018 Nobel Prize in Medicine on October 2nd, immunotherapy is a burgeoning area in cancer therapy. However, what does it involve precisely? And where did it originate? Explanation with Jean-François Moreau, Professor of Immunology at the University of Bordeaux and Immunoconcept laboratory researcher.
Two immunologists, James P. Allison from the USA and Tasuku Honjo from Japan, were awarded the Noble Prize in Medicine for their research on cancer therapy by "Inhibition of negative immune regulation". This is a hot topic at the moment, embodying hope to improve the treatments and care of cancer patients.
Cancer and immunology, a long history
Cancer and immunology are very closely linked and the idea of involving the immune system in cancer therapy is not new. Already in the late 19th century, it had been observed that, in some cases, cancer regression could occur in cases of severe infectious disease.
Later, in the 1950s, the concept of immunological surveillance put forward by the Australian virologist Burnet recognized the major role of the immune system in tumor proliferation control. This concept was revisited by the American researcher Robert Schreiber in 2006 who discovered that interaction between the immune system and the tumor cell can lead to three phases of cancer cell survival. The first is the "elimination" phase; these cells will no longer be able to produce tumors in the vast majority of cases (although tumors are known to regress spontaneously).
The second phase is a state of "equilibrium"; the immune system controls tumor cell proliferation without inducing the eradication of these cells. The third phase is the tumor cell "escape" phase from immunological control by a number of mechanisms. This phase is the only one to be clinical visible, and is that which is commonly referred to as cancer and indicates that the immune system has become ineffective in controlling tumor growth. This is widely known as the 3E theory.
The key word: equilibrium
"The idea behind immunotherapy is not necessarily that of eliminating the tumor, but restoring equilibrium in favor of the host carrier by acting upon the patient's immune defenses" explains the professor. The aim is not to combat and destroy the tumor at all costs, but merely to execute a regulation phenomenon that is unfavorable for the tumor. This is the promise held by therapies that will utilize monoclonal antibodies. These antibodies are molecules naturally produced by the immune system with a view to triggering a targeted attack on a previously encountered danger, similar to how a vaccine would provide protection against an infectious disease.
"Not that long ago, these antibodies were only used for targeting essential tumor-specific proteins that they succeeded in destroying effectively. However, once the tumor cells stop expressing the target protein, they elude the efficacy of the treatment" acknowledges Jean François Moreau. "It doesn't always work", notes the expert, "but when it does, it works very well".
A future full of promise
Indeed, despite being very effective and providing a long-term effect after treatment has stopped, immunotherapy cannot yet be applied to all cancers, as not all tumors are the same. The causes of these failures are not all known, but one of the objectives of current clinical research is to characterize, using biomarkers, patients for whom these very costly therapies have beneficial effects. "As these applications follow on from fundamental research on knowledge of immune system function, further work needs to be accomplished in this area" acknowledges the immunologist.
"We now have evidence that targeting the immune system can be a very effective and relatively straightforward way of treating cancer. Many avenues have yet to be explored, but we know that it is essentially within our grasp to obtain effective therapies in the long-term, with quite modest and perfectly manageable adverse effects" concludes Jean-François Moreau.