Toward immunotherapies tailored to each patient
Dr Delphine Loirat, oncologue médicale, spécialiste des essais clinique en immunothérapie, porteur du projet Centre d’immunothérapie, à l'Institut Curie, Paris.
Whether used to treat existing cancer or prevent development of a cancer, cancer vaccines work by teaching the immune system. The first step is identifying a factor that can teach it to recognise the danger to be eliminated. “Tumour cells are your own cells gone out of control, however,” explains Dr. Delphine Loirat, “so the challenge is in targeting an attack against them without destroying the healthy tissue they came from.” The Holy Grail of vaccine therapy against cancer consists of identifying a factor that is specific enough to the tumour to trigger an immune response that is effective but causes little or no damage to biologically similar tissues.
Vaccinating activates the T lymphocytes (or T cells) so they can destroy an enemy. The way to do this is by showing them a fragment of the enemy, usually a representative piece of a protein, which in turn is specific to the pathogen or tumour cells to be eliminated. This bait, called an epitope, sends the T lymphocytes after the dangerous cells. In a tumour cell, the epitope may take several forms. “Any protein fragment can serve this purpose,” clarifies the immunologist. “The real feat is finding one that is specific to the tumour, meaning one that has resulted from a mutation of a specific gene in the tumour cell (one characteristic of tumour cells being that they accumulate mutations within their genome. That’s what immunologists refer to as a neoepitope.” Identifying them is one of the prerequisites to developing a targeted, effective response against tumours. That is the goal of the clinical trial launched in late May 2016 by Delphine Loirat and Eliane Piaggio, joint directors of the Translational Immunotherapy (TransIm) research team (SiRiC, Institut Curie). The trial, which offers no direct benefits to the patients involved, aims to determine the feasibility of identifying these neoepitopes from the tumour cells invading the ganglia and looking in the blood, ganglia, and tumour for T lymphocytes that recognise the neoepitopes. Up to now, neoepitopes have been “deduced” using computer algorithms based on mutations present in the tumours. “By collaborating with other Institut Curie specialists, including surgeons, we will be able to search the ganglia invaded by tumour cells in 20 patients with breast cancer and 20 patients with skin melanoma for the presence of neoepitopes.” This offers real hope for developing cancer vaccines, since neoepitopes make it possible to develop vaccines tailored for each patient, specific enough to trigger a response against the tumour with little toxicity to healthy tissues. Neoepitopes open the door to individualised, or personalised, immunotherapies.