In short
Autologous peripheral blood-derived CD4 T-cells CRISPR-edited at the CD40LG locus are an investigational cell therapy being studied for X-linked hyper IgM syndrome type 1 (HIGM1), a rare inherited immune disorder. The substance is also known by the development code FT018 and is being developed by Fondazione Telethon. One Phase 1/2 clinical trial is currently authorised in the EU, with a planned enrollment of 6 participants, to evaluate the safety of this gene-edited cell therapy.
Key points
- Phase 1/2 clinical trial authorised in the EU for X-linked hyper IgM syndrome type 1 (HIGM1)
- 6 participants are planned to be enrolled in this open-label, single-arm study
- The therapy uses CRISPR/Cas9 gene editing to correct the CD40LG gene in the patient's own CD4 T-cells
- Given as a dispersion for intravenous infusion, prepared from the patient's own blood cells
- The primary outcome measures dose-limiting toxicities after each dose of the drug product
- The substance has orphan designation and no marketing authorisation — it is still investigational
What is autologous CD4 T-cells CRISPR-edited at the CD40LG locus?
Autologous peripheral blood-derived CD4 T-cells CRISPR-edited at the CD40LG locus, also referred to as FT018, is an investigational cell therapy. The term autologous means that the cells come from the patient's own body. The therapy consists of CD4 T-cells — a type of immune cell — that have been genetically modified using CRISPR/Cas9 gene-editing technology at the CD40LG gene locus. The substance is classified as a cell therapy and is given as a dispersion for infusion. It has no marketing authorisation in the product records and is therefore still an investigational substance. The therapy has been granted orphan designation, meaning it targets a rare disease. The product is supplied by Fondazione Telethon.
How does autologous CD4 T-cells CRISPR-edited at the CD40LG locus work?
The therapy is designed for patients with X-linked hyper IgM syndrome type 1 (HIGM1), a genetic disorder caused by mutations in the CD40LG gene. This gene normally provides instructions for making a protein called CD40 ligand, which is essential for communication between immune cells. In HIGM1, the defective gene means that CD4 T-cells cannot properly activate other immune cells, leaving patients vulnerable to infections. The investigational therapy takes the patient's own CD4 T-cells and edits them outside the body (ex vivo) at the CD40LG locus using CRISPR/Cas9 and an IDLV-based vector, with the aim of restoring the function of the CD40LG gene.
Which conditions is it used or studied for?
- X-linked immunodeficiency with hyper-IgM type 1 (HIGM1) — a rare inherited immune disorder in which the body cannot produce certain classes of antibodies properly, leading to recurrent and severe infections. This is the condition studied in the authorised trial.
How is autologous CD4 T-cells CRISPR-edited at the CD40LG locus given?
The therapy is prepared as a dispersion for infusion and is administered by intravenous infusion, meaning it is given directly into a vein. The cells are collected from the patient's own peripheral blood, edited in a laboratory, and then returned to the patient through an infusion. The trial also involves several vaccines given by intramuscular injection as part of the study procedures, including TICOVAC (tick-borne encephalitis vaccine), Rabipur (rabies vaccine), and Infanrix hexa (a combined vaccine against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, and Haemophilus influenzae type b).
What do the clinical trials show?
One clinical trial is authorised in the EU for this investigational therapy. The study is an open-label, single-arm, Phase 1/2 trial, meaning that both the researchers and the participants know what treatment is being given, and all participants receive the investigational therapy.
The trial plans to enroll 6 participants with X-linked hyper IgM syndrome type 1. The primary outcome measures the proportion of patients experiencing dose-limiting toxicities (DLTs) after each dose of the drug product. Dose-limiting toxicities are side effects severe enough to prevent increasing the dose. The main aim of the study is to evaluate the safety of the treatment with FT018 in patients with HIGM1.
The trial is currently in the authorised status, which means it has received regulatory approval to proceed but may not yet have begun recruiting participants. The study also administers several vaccines to participants as part of the trial procedures, to assess immune responses.
What side effects are known?
The trial is designed to measure side effects, specifically dose-limiting toxicities, as its primary outcome. However, no side effect data from completed studies are available in the provided sources, as this is an early-phase trial that is still authorised rather than completed. The safety profile of the therapy will be established through this and future studies.