Immunotherapy

Stimulating and redirecting the patient's immune defenses to help fight cancer is the key principle of immunotherapy treatments, the development of which has revolutionized oncology over the last fifteen years. As a key player in this field, Institut Curie actively participates in the development of research and treatment protocols using immunotherapy.
How does it work? As a general rule, the immune system recognizes cancer cells as foreign and can eliminate them; this process is effective most of the time. But sometimes cancer develops thanks to new properties acquired by tumor cells, enabling them to block or bypass these defenses. Immunotherapy involves redirecting the patient's immune system so that it restores the fight against the tumor.

This therapeutic approach offers several advantages:

• It is specific to the patient's immune system; side effects are more limited, and if they do occur, they are usually easier to bear than those associated with chemotherapy. However, immunotherapy treatments are often combined with conventional chemotherapies.
• Interestingly, the benefits of immunotherapy are often prolonged over time. 25-30% of patients treated with immunotherapy (all cancers combined) show a prolonged response after treatment. These figures vary widely from one cancer and one patient to another.

There are several types of immunotherapy treatment already available or in development, including: 

• immune checkpoint inhibitors
• CAR-T Cells
• vaccines.

Immune checkpoint inhibitors

There are several receptors on the surface of cancer cells and immune cells which, when they interact, have a "checkpoint" action that inhibits the anti-tumor action of the immune system. It's as if the cancer cells become invisible to the immune system.

In concrete terms, this mainly involves:

• PD-1 receptors on the surface of T-lymphocyte immune cells, which interact with PD-L1 receptors on the surface of cancer cells and other antigen-presenting immune cells.
• CTLA-4 receptors on the surface of T lymphocytes, which interact with antigen-presenting cells.

Anti-checkpoint drugs are laboratory-produced antibodies that specifically target certain receptors on the surface of immune cells or cancer cells. They block the interaction between the tumor cell and the immune cell, thus restoring the immune system's anti-tumor action.

In concrete terms, these are essentially:

• anti-PD-1 agents such as nivolumab, pembrozilumab and cemiplimab
• anti-PD-L1 agents such as atezolizumab, avelumab, durvalumab
• anti-CTLA-4 agents such as ipilimumab.

These treatments are administered by intravenous injection at regular intervals, depending on the disease being treated and each antibody.

CAR-T cells

Cell and gene therapies - including CAR-T (Chimeric Antigen Receptor) cells - are extremely promising new forms of immunotherapy that have gained momentum over the last 10 years. They involve harvesting a particular type of immune cell from a patient, specifically T lymphocytes, then genetically modifying them in the laboratory so that they are capable of specifically recognizing and destroying cancer cells, and finally re-administering them to the patient himself. This strategy is currently used to combat certain blood cancers, such as leukemia in children and young adults, and lymphoma in adults.
At Institut Curie, the CellAction cell and gene therapy platform, part of the PSCC (Paris Saclay Cancer Cluster), is a first-of-its-kind facility in France, combining highly qualified scientific, clinical and technical expertise with state-of-the-art equipment. CellActions doctors and researchers explore and design optimized cell and gene therapy strategies, more effective in a wider range of indications, including solid tumors.

Research and vaccines

Immunotherapy research is a priority for Institut Curie. Institut Curie's immunotherapy center implements an integrated approach involving all stakeholders: physicians, researchers, nurses and research coordinators. The main aims of the Cancer Immunotherapy center are as follows:

• To implement early trials and study combinations of treatments that could improve therapeutic effectiveness.
• Discover new predictive biomarkers of response to treatment.
• Understand the mechanisms of immunotherapy and why some patients respond and others don’t.

In addition, several research and medical teams have entered the field of vaccination and are working on the development of therapeutic vaccines:

• Determining the genetic and epigenetic characteristics of each tumor
• Identifying new therapeutic targets against which to direct the immune system
• Designing "tailor-made" vaccines, specific to each patient's tumor.