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Autologous Cd34+ Cells Transduced With The G1Xcgd Lentiviral Vector Containing The Human Cybb Gene

This article discusses an innovative gene therapy approach for treating X-Linked Chronic Granulomatous Disease (X-CGD). The treatment involves using autologous CD34+ cells transduced with the G1XCGD lentiviral vector containing the human CYBB gene. This phase I/II clinical trial aims to evaluate the safety and efficacy of this gene therapy in patients with X-CGD, potentially offering a new treatment option for this rare genetic disorder.

Table of Contents

What is this treatment?

The treatment we’re discussing is a complex medical procedure known as AUTOLOGOUS CD34+ CELLS TRANSDUCED WITH THE G1XCGD LENTIVIRAL VECTOR CONTAINING THE HUMAN CYBB GENE. It’s also known by the simpler name OTL-102[1]. This is a type of gene therapy, which means it involves modifying a person’s genes to treat or cure a disease.

How does it work?

This treatment works in several steps:

  1. Cell collection: First, doctors collect special cells called CD34+ cells from the patient’s own body. These are a type of stem cell that can develop into different types of blood cells.[1]
  2. Gene modification: Then, in a laboratory, these cells are modified using a tool called a lentiviral vector. This vector carries a healthy copy of the CYBB gene (also known as gp91phox) into the cells.[1]
  3. Cell return: Finally, these modified cells are given back to the patient through an intravenous (IV) injection.[1]

The goal is for these modified cells to produce healthy blood cells that can fight infections properly.

What condition does it treat?

This treatment is being developed for X-linked Chronic Granulomatous Disease (X-CGD). This is a rare genetic disorder that affects the immune system.[1]

In X-CGD, certain immune cells called phagocytes can’t effectively kill certain bacteria and fungi. This leads to severe, recurrent infections and inflammatory problems. The ‘X-linked’ part means it primarily affects males.[1]

Current Clinical Trial

This treatment is currently being studied in a clinical trial. The trial is described as a “phase I/II, non-randomized, monocentric open-label study.”[1] Let’s break down what this means:

  • Phase I/II: This means the trial is testing both safety and how well the treatment works.
  • Non-randomized: All participants receive the same treatment; there’s no placebo group.
  • Monocentric: The study is being conducted at a single medical center.
  • Open-label: Both the researchers and participants know what treatment is being given.

Who is eligible for the trial?

The trial has specific criteria for who can participate. Here are some key points:[1]

  • Male patients with X-CGD, typically over 23 months old (younger patients may be considered in some cases)
  • Patients must have a confirmed molecular diagnosis of X-CGD
  • Patients must have a severe ongoing infection or be at high risk of infection despite conventional therapy
  • Patients should not have an available HLA-matched donor for a bone marrow transplant
  • Patients must not have HIV, hepatitis B, or hepatitis C

There are also several exclusion criteria, such as contraindications to certain procedures or medications involved in the treatment.

What are the objectives of the trial?

The main goal of this trial is to evaluate how safe and effective this treatment is. Specifically, researchers want to see if it can restore the function of certain immune cells and if this improvement lasts for at least 12 months.[1]

Secondary objectives include:[1]

  • Evaluating clinical efficacy, particularly in improving immunity against bacterial and fungal infections
  • Assessing how well the gene transfer process works
  • Studying how the modified cells establish themselves and persist in the body over time

What are the endpoints of the trial?

The trial has several “endpoints” or outcomes that it will measure to determine if the treatment is successful:[1]

  • Primary endpoints:
    • Safety: Measuring any adverse events related to the treatment
    • Efficacy: Checking if at least 5% of certain immune cells (granulocytes) are functioning correctly after 12 months
  • Secondary endpoints:
    • Improvements in nutritional status, growth, and development
    • Clearing of pre-existing infections or inflammatory problems
    • Measuring the percentage of modified cells in the blood over time
    • Assessing overall improvements in immune function and ability to fight infections

This trial represents an important step in developing a potential new treatment for X-linked Chronic Granulomatous Disease, a serious genetic disorder affecting the immune system.

Aspect Details
Trial Type Phase I/II, non-randomized, monocentric open-label study
Treatment Autologous CD34+ cells transduced with G1XCGD lentiviral vector
Condition X-linked Chronic Granulomatous Disease (X-CGD)
Main Objective Evaluate safety and efficacy of gene therapy
Primary Endpoints 1. Safety (adverse events incidence)
2. Efficacy (≥5% functioning neutrophils at 12 months)
Key Eligibility Male X-CGD patients >23 months, severe ongoing infections, no HLA-matched donor
Exclusion Criteria HLA-identical donor available, contraindications for leukapheresis or conditioning
Secondary Objectives 1. Clinical efficacy against infections
2. Transduction of CD34+ cells
3. Evaluation of engraftment and stability

FAQ

  • What is X-Linked Chronic Granulomatous Disease (X-CGD)? X-CGD is a rare genetic disorder that affects the immune system. It is caused by a defect in the CYBB gene, which leads to impaired function of certain white blood cells, making patients more susceptible to severe bacterial and fungal infections.
  • How does the G1XCGD gene therapy work? The therapy involves collecting the patient's own CD34+ blood stem cells, modifying them with a lentiviral vector containing the correct CYBB gene, and then returning these cells to the patient. This aims to restore the normal function of white blood cells and improve the patient's immune system.
  • Who is eligible for this clinical trial? The trial is primarily for male X-CGD patients over 23 months of age, with some exceptions for younger patients. Participants must have a confirmed molecular diagnosis and severe ongoing infections or inflammatory complications despite conventional therapy.
  • What are the main objectives of this clinical trial? The main objectives are to evaluate the safety of the treatment and its efficacy in restoring the function of neutrophils (a type of white blood cell). The trial also aims to assess the long-term stability of the gene-modified cells and improvements in the patient's overall health.
  • How is the effectiveness of the treatment measured? The primary measure of efficacy is the restoration and stability of functioning neutrophils, assessed by a test called DHR (dihydrorhodamine). The trial looks for at least 5% of cells expressing the corrected gene at 12 months post-treatment.

Ongoing Clinical Trials on Autologous Cd34+ Cells Transduced With The G1Xcgd Lentiviral Vector Containing The Human Cybb Gene

  • Study of G1XCGD Lentiviral Vector in Patients with X-Linked Chronic Granulomatous Disease

    Not recruiting

    2 1 1
    Investigated diseases:
    Investigated drugs:
    France

Glossary

  • Autologous: Using cells or tissues obtained from the same individual. In this context, it means using the patient's own blood stem cells for the gene therapy.
  • CD34+ cells: A type of blood stem cell that can develop into all types of blood cells, including white blood cells important for fighting infections.
  • Lentiviral vector: A tool used in gene therapy to deliver genetic material into cells. It's derived from a type of virus but modified to be safe for therapeutic use.
  • CYBB gene: The gene that, when defective, causes X-linked Chronic Granulomatous Disease. It provides instructions for making a protein important for immune cell function.
  • X-linked Chronic Granulomatous Disease (X-CGD): A rare genetic disorder affecting the immune system, causing recurrent severe infections and inflammatory problems.
  • NADPH oxidase: An enzyme complex in certain white blood cells that helps fight infections. It's defective in patients with X-CGD.
  • DHR test: Dihydrorhodamine test, used to measure the function of neutrophils (a type of white blood cell) in patients with X-CGD.
  • HLA matching: A process of finding a donor whose human leukocyte antigens (HLA) closely match the patient's. Important for transplant procedures.
  • Leukapheresis: A medical procedure to separate and collect specific white blood cells from the blood.
  • Conditioning regimen: A treatment given before cell therapy to prepare the patient's body, often involving chemotherapy or radiation.

References

  1. http://clinicaltrials.eu/trial/study-of-g1xcgd-lentiviral-vector-in-patients-with-x-linked-chronic-granulomatous-disease/