From Predisposing Genetic Variants to Public (Shared) Tumor-Specific Neoantigens in Uveal Melanoma
Abstract
Melanomas do not only affect the skin. They also appear in the inner part of the eye, and this type of tumor is called uveal melanoma (UM). Each year, around 3,500 patients are diagnosed with UM in the United States. UM can often be treated effectively when localized in the eye, but one third to one half of the patients will eventually develop metastases, mostly in the liver. Patients suffering from UM metastases face limited treatment options and have a dismal prognosis, as most of them will die of their cancer. UM often occurs in individuals with a light eye color and a fair skin, which makes it much more common in individuals of European ancestry. Patients are usually between age 55 and 70, with a slight preponderance of males. Since U.S. military Veterans are predominantly men of European ancestry between the ages of 50 and 79, it is expected that, among the approximately 20 million Veterans, more than 100 will be diagnosed with UM each year. A dramatic increased risk in Veterans has been reported, but not yet demonstrated. UM is therefore a serious concern for U.S. military active-duty Service Members and Veterans as well as a serious health problem for the American public in general. UM patients face several critical unmet needs, including (i) a better understanding of the causes of UM to address questions such as why me? and is it due to my personal or professional activities, including in the U.S. military? (ii) a better estimation of their risk to develop metastases to address questions such as will the cancer recur? and (iii) better treatments, especially for patients with metastases. To address these questions, three research groups highly-specialized in UM from Institut Curie (Paris, France) will tackle different but complementary aspects of the disease: geneticists (Dr M.H. Stern, Principal Investigator) studying the causes of UM that are inherited (transmitted from parents to children); biologists (Dr M. Rodrigues, Project Leader) aiming to understand how UM develops over time; immunologists (Dr O. Lantz, Project Leader) to explore how we can stimulate the patient s immune defenses (the white blood cells that should destroy the tumor cells) to treat UM. Altogether, we aim to bridge the gap between genetics, biology, and immunology. The Institut Curie Research Center gathers top-level UM research labs with all the equipment needed for cutting-edge experiments. The Institut Curie Hospital is a major clinical center for UM worldwide and the top recruiter site in several UM clinical trials, including in the trial that led to the recent approval of Tebentafusp, the first drug specifically approved for UM patients. Most of our UM patients have already consented to use their clinical data and biological samples for research. Thanks to this priceless gift, we have now stored more than 2,000 tumor and blood samples. For instance, we can use tumor samples to grow tumors in Petri dishes (called cell lines) or on mice (called xenografts). Importantly, we consider that sharing our results and discussing our priorities in research with UM patients is essential. Therefore, we organize yearly meetings for UM patients (~200 attendees). Furthermore, this new project is built together with the patient organization MPNErare (Melanoma Patient Network Europe for rare melanomas), a longstanding partner. Our research program has the potential to have a tremendous impact both on the scientific community and on patients and relatives. For the patients and their relatives, our program will directly allow (i) to find new inherited causes that increase the risk of developing a UM, which will be integrated into clinical practice to closely follow families where UM is expected to be more frequent, (ii) to create a new tool from a simple blood sample to estimate the risk of suffering metastases, and (iii) to find new ways to stimulate the immune system to develop innovative therapies such as vaccines against
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310722
Entities
People
- Marc-henri Stern
Organizations
- Curie Institute
- United States Army