T-cells are a type of white blood cell and are the key players of the adaptative immune system. They develop from stem cells in the bone marrow and then travel to the thymus to complete their development. They are called ‘T-cell progenitors’ until they reach the thymus. T-cells move around the body to find and destroy dangerous cells such as those infected by pathogens or tumour cells. They are an elite force that protects the body from infections and cancers.
The thymus is a small butterly-shaped lymphoid organ located in the upper chest. Its role is to educate T-cell progenitors to become mature, specialized T-cells. The thymus ensures that T-cells do not attack the self and can recognize more than 200 million potential foreign particles such as viruses, bacteria, fungi and malignant cells. Most T-cells are produced before birth or during childhood and adolescence. Once you reach puberty, the thymus starts to slowly shrink and become replaced by fat. At 25 years old, the thymus has already lost around 40% of its capacity, causing the body to become more vulnerable to infections and cancers. Smart Immune is investigating ways to reverse this involution.
The failure of the immune system to function as it should, can result from immune deficiencies present at birth, acquired diseases such as blood cancers, medications that suppress or damage the immune system, unnecessary or over-the-top immune responses such as allergies, or immune responses to one's self, called autoimmunity.
HSCT is the transplantation of stem cells, usually derived from the bone marrow, peripheral blood, or umbilical cord blood, to produce additional normal healthy blood cells, including T-cells. It is a therapeutic option for treating several serious blood cancers and some other conditions. HSCT may be autologous (the patient's stem cells are used) or allogeneic (the stem cells come from a donor). Allogeneic HSCT carries significant risks such as rejection of the graft, infection, graft versus host disease (GVHD), and potential long-term side effects, translating into a 50% morbidity and mortality rate at 3 years post HSCT.
Patients with severe T-cell deficiencies are vulnerable to infections and cancers. Rearming their immune system with a new compartment of fully functional T-cells would allow them to defend themselves against any threats.
T-cell therapies can be manufactured from different materials (mature T-cells, stem cells, possibly induced pluripotent stem cells) and from different sources (the patient or a donor). Smart Immune is the first company to develop thymus-empowered allogeneic T-cell therapies and advance them into clinical testing through its T-cell progenitor platform, ProTcell.
T-cells don’t always recognize the difference between cancer and normal cells as some malignant cells have strategies to look harmless and so evade detection. Researchers are working to train T-cells to recognize specific types of cancer by developing CAR T-cell therapies. CAR means ‘chimeric antigen receptor’. CAR T-cell therapies can be compared to a personalized radar that target a specific type of cancer. Several CAR T-cell therapies are already on the market and available for patients in the USA and the European Union.
Smart Immune is working to improve the prognosis of immune-compromised patients with life-threatening diseases such as high-risk blood cancers and primary immunodeficiencies.
ProTcell is Smart Immune’s thymus-empowered T-cell therapy platform to fully and rapidly re-arm the immune system, aimed at enabling next-generation allogeneic T-cell therapies for all. The ProTcell platform has the potential for enabling a broad range of future applications including CAR ProTcell for allogeneic, long-lasting, targeted immuno-oncology therapies.
Smart Immune’s ProTcell platform is designed to reconstitute a T-cell compartment in around three months , compared with 12-18 months through the standard HSCT approach, significantly reducing the time to full immune recovery and possibly opening access to allogeneic medicine to more patients.
Smart Immune is in clinical trials, working with top-tier EU and US academic partners. The lead ProTcell application, Smart 101/102, is in Phase I/II trials and is generating encouraging data. Please refer to the Pipeline and News sections to learn more.
Smart Immune announced in October 2022 that SMART102, a human T-cell progenitor cell injection derived from cord blood using the ProTcell platform, has entered clinical testing with the first adult patient treated.
In January 2023, the company announced the successful dosing of the first adult leukemia patient with SMART101, in a trial sponsored by Smart Immune at Memorial Sloan Kettering (MSK) in New York. No related adverse event has been reported.
In addition to MSK, Smart Immune is a research and clinical partner with Greater Paris University Hospitals (AP-HP), including Necker-Enfants Malades Hospital and the Imagine Institute. Our sponsored clinical trials are multicentred with participants in Europe and the US, such as the Bambino Gesù Hospital in Rome and the Texas Children’s Hospital in Houston.
Smart Immune’s ProTcell platform is in the early stages of clinical evaluation. For now, its thymus-empowered therapies are only available through clinical trials.
Since being founded in 2017, Smart Immune has raised €22 million from family offices and public grants.