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Autologous T-Cells Transduced With Lentiviral Vector Expressing A Chimeric Antigen Receptor Directed Against Cd19

This article explores the use of autologous T-cells transduced with a lentiviral vector expressing a chimeric antigen receptor (CAR) directed against CD19 in clinical trials. This innovative therapy, known as CAR T-cell therapy, is being investigated for various conditions, including relapsed or refractory B-cell malignancies and certain autoimmune diseases. The trials aim to assess the safety, efficacy, and feasibility of this personalized treatment approach in patients who have not responded well to conventional therapies.

Table of Contents

Overview

AUTOLOGOUS T-CELLS TRANSDUCED WITH LENTIVIRAL VECTOR EXPRESSING A CHIMERIC ANTIGEN RECEPTOR DIRECTED AGAINST CD19, also known as MB-CART19.1 or CD19-CAR_Lenti, is an innovative cell therapy being investigated for the treatment of various conditions[1][2][3][4]. This therapy belongs to a class of treatments called CAR T-cell therapy, which harnesses the power of a patient’s own immune system to fight diseases.

Mechanism of Action

The treatment involves taking T-cells (a type of immune cell) from the patient’s own body and genetically modifying them in a laboratory. These modified T-cells are equipped with a special receptor called a chimeric antigen receptor (CAR) that targets CD19, a protein found on the surface of certain cells[1][2][3][4].

The process involves the following steps:

  1. T-cells are collected from the patient’s blood through a process called leukapheresis.
  2. The T-cells are genetically modified using a lentiviral vector, which introduces the CAR gene into the cells.
  3. The modified T-cells are grown and multiplied in the laboratory.
  4. The patient receives chemotherapy to prepare their body for the treatment.
  5. The modified CAR T-cells are infused back into the patient’s body.

Once in the body, these CAR T-cells can recognize and attack cells that express CD19, potentially eliminating diseased cells while sparing healthy ones[1][2][3][4].

Conditions Treated

MB-CART19.1 is being investigated for the treatment of several conditions, including:

  • B-cell malignancies: This includes various types of blood cancers such as:
    • Acute Lymphoblastic Leukemia (ALL)
    • Non-Hodgkin’s Lymphoma (NHL)
    • Chronic Lymphocytic Leukemia (CLL)
    • Acute Myeloid Leukemia (AML) expressing CD19
  • Autoimmune diseases: The therapy is also being explored for treating certain autoimmune conditions, including:
    • Systemic Lupus Erythematosus (SLE)
    • Systemic Sclerosis (SSc)
    • Dermatomyositis/Polymyositis (DM/PM)

These conditions are typically treated when they are refractory (resistant to standard treatments) or relapsed (have returned after initial treatment)[1][2][3][4].

Administration

MB-CART19.1 is administered as an intravenous infusion. Before the infusion, patients typically receive a conditioning chemotherapy regimen, which may include drugs like cyclophosphamide and fludarabine. This chemotherapy helps prepare the body to receive the CAR T-cells[1][3].

The dose of CAR T-cells can vary, but one study mentioned a target dose of 1 x 106 cells per kg of body weight[1].

Efficacy

As MB-CART19.1 is still in clinical trials, its full efficacy is yet to be determined. However, the ongoing studies are designed to assess various efficacy measures, including:

  • Overall response rate (ORR)
  • Complete remission (CR) rate
  • Minimal residual disease (MRD) response
  • Duration of response
  • Disease-free survival
  • Overall survival

These outcomes will be evaluated at different time points, such as day 28, month 3, and up to 1 year after treatment[3].

Safety and Side Effects

As with any advanced therapy, MB-CART19.1 may cause side effects. Some potential side effects being monitored in clinical trials include:

  • Cytokine Release Syndrome (CRS): A condition where the immune system becomes highly activated, potentially causing fever, low blood pressure, and other symptoms.
  • CAR T-cell Associated Neurotoxicity Syndrome (ICANS): Neurological side effects that may occur after CAR T-cell therapy.
  • Infections
  • Leukopenia (low white blood cell count)
  • Hypogammaglobulinemia (low antibody levels)

The severity of these side effects is being closely monitored in clinical trials[2][4].

Ongoing Research

Several clinical trials are currently underway to further investigate the safety and efficacy of MB-CART19.1 in various conditions:

  • A phase I/II study in patients with relapsed or refractory CD19-positive B-cell malignancies, including ALL, NHL, and CLL[3].
  • A study investigating its use in refractory or relapsed acute myeloid leukemia (AML) expressing CD19[1].
  • A trial exploring its potential in treating autoimmune diseases such as systemic lupus erythematosus, systemic sclerosis, and dermatomyositis/polymyositis[4].

These studies aim to determine the optimal dose, assess safety profiles, and evaluate the effectiveness of MB-CART19.1 in various patient populations.

Aspect Details
Therapy Name MB-CART19.1 (CD19 CAR transduced T cells)
Type of Therapy Autologous CAR T-cell therapy
Target CD19 protein on B-cells
Conditions Studied Relapsed/refractory B-cell malignancies (ALL, NHL, CLL), Systemic Lupus Erythematosus, Systemic Sclerosis, Dermatomyositis/Polymyositis
Administration Intravenous infusion
Trial Phases Phase I/II
Primary Objectives Safety assessment, dose determination, efficacy evaluation
Key Endpoints Incidence of adverse events, overall response rate, CAR T-cell persistence
Potential Side Effects Cytokine Release Syndrome, Neurotoxicity, B-cell depletion, Infections
Patient Eligibility Varies by trial; generally includes refractory/relapsed status, specific disease criteria, adequate organ function

FAQ

  • What is CAR T-cell therapy? CAR T-cell therapy is a type of immunotherapy where a patient's own T-cells are genetically modified to express a chimeric antigen receptor (CAR) that targets specific proteins on cancer cells or other harmful cells. In this case, the CAR targets CD19, a protein found on certain types of B-cells.
  • What conditions are being studied with this CAR T-cell therapy? The clinical trials are investigating the use of CD19-targeted CAR T-cells for relapsed or refractory B-cell malignancies (such as acute lymphoblastic leukemia and non-Hodgkin lymphoma) and certain autoimmune diseases (including systemic lupus erythematosus, systemic sclerosis, and dermatomyositis/polymyositis).
  • How is the CAR T-cell therapy administered? The therapy is administered through intravenous infusion. Before the infusion, patients typically receive conditioning chemotherapy to prepare their body for the CAR T-cells.
  • What are the main objectives of these clinical trials? The main objectives include assessing the safety and tolerability of the CAR T-cell therapy, determining the recommended dose, evaluating its efficacy in treating the target conditions, and studying the persistence of CAR T-cells in the body over time.
  • What are some potential side effects of CAR T-cell therapy? Potential side effects being monitored include cytokine release syndrome (CRS), CAR T-cell associated neurotoxicity syndrome (ICANS), infections, and B-cell depletion. The trials are carefully assessing the incidence and severity of these effects.

Ongoing Clinical Trials on Autologous T-Cells Transduced With Lentiviral Vector Expressing A Chimeric Antigen Receptor Directed Against Cd19

  • A Study Testing Anti-CD19 CAR T-Cell Therapy in Patients with Systemic Sclerosis Who Did Not Respond to Immunosuppressive Drugs

    Recruiting

    2 1 1
    Investigated diseases:
    Investigated drugs:
    France

  • Study on the Safety of MB-CART19.1 for Patients with Active Systemic Lupus Erythematosus, Systemic Sclerosis, or Dermatomyositis/Polymyositis

    Recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    Germany

  • Study on Anti-CD19 CAR T-Cell Therapy for Patients with Refractory Systemic Autoimmune Diseases Using Levetiracetam, Fludarabine, and a Drug Combination

    Recruiting

    1 1 1 1
    Investigated diseases:
    Investigated drugs:
    Italy

  • Study on the Safety of CD19 CAR-T Cells, Cyclophosphamide, and Fludarabine in Adults with Refractory or Relapsed Acute Myeloid Leukemia Expressing CD19

    Recruiting

    1 1 1 1
    Investigated drugs:
    France

  • Long-Term Safety Study of MB-CART19.1, MB-CART20.1, and Zamtocabtagene Autoleucel for Patients with Advanced Melanoma or B-Cell Malignancies

    Recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    Germany

  • Study of CD19-CAR_Lenti, Fludarabine, and Cyclophosphamide in Children with Relapsed or Refractory Acute Lymphoblastic Leukemia or Aggressive B-Cell Lymphomas

    Not recruiting

    2 1 1 1
    Investigated diseases:
    Investigated drugs:
    Italy

  • Study on MB-CART19.1 for Patients with Relapsed or Refractory CD19 Positive B Cell Malignancies

    Not recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    Germany

Glossary

  • Autologous: Derived from the patient's own cells or tissues. In this context, it refers to T-cells taken from the patient's own body.
  • Chimeric Antigen Receptor (CAR): A specially engineered receptor added to T-cells that allows them to recognize and attack specific target cells.
  • CD19: A protein found on the surface of B-cells, which is targeted by the CAR T-cells in these studies.
  • Lentiviral Vector: A tool used to deliver genetic material into cells, derived from a type of virus called a lentivirus.
  • T-cells: A type of white blood cell that plays a central role in the immune response.
  • B-cells: Another type of white blood cell that produces antibodies and is involved in the immune response.
  • Refractory: Resistant to treatment; a condition that does not respond to standard therapies.
  • Relapsed: The return of a disease or symptoms after a period of improvement.
  • Cytokine Release Syndrome (CRS): A potential side effect of CAR T-cell therapy where the immune system becomes overly activated, causing symptoms like fever and low blood pressure.
  • CAR T-cell Associated Neurotoxicity Syndrome (ICANS): A potential neurological side effect of CAR T-cell therapy that can cause confusion, difficulty speaking, or seizures.
  • Systemic Lupus Erythematosus (SLE): An autoimmune disease that can affect various parts of the body, including skin, joints, kidneys, and other organs.
  • Systemic Sclerosis (SSc): An autoimmune disease characterized by hardening and tightening of the skin and connective tissues.
  • Dermatomyositis/Polymyositis (DM/PM): Inflammatory diseases that cause muscle weakness and skin rashes.
  • Acute Lymphoblastic Leukemia (ALL): A type of blood cancer that affects lymphocyte-forming cells in the bone marrow.
  • Non-Hodgkin Lymphoma (NHL): A group of blood cancers that develop from lymphocytes.

References

  1. http://clinicaltrials.eu/trial/study-on-the-safety-of-cd19-car-t-cells-cyclophosphamide-and-fludarabine-in-adults-with-refractory-or-relapsed-acute-myeloid-leukemia-expressing-cd19/
  2. http://clinicaltrials.eu/trial/study-on-anti-cd19-car-t-cell-therapy-for-patients-with-refractory-systemic-autoimmune-diseases-using-levetiracetam-fludarabine-and-a-drug-combination/
  3. http://clinicaltrials.eu/trial/study-on-mb-cart19-1-for-patients-with-relapsed-or-refractory-cd19-positive-b-cell-malignancies/
  4. http://clinicaltrials.eu/trial/study-on-the-safety-of-mb-cart19-1-for-patients-with-active-systemic-lupus-erythematosus-systemic-sclerosis-or-dermatomyositis-polymyositis/