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Autologous T-Cells Ex Vivo Modified With A Lentiviral Vector Encoding A Chimeric Antigen Receptor Specific For Cd1A

This article discusses a groundbreaking clinical trial investigating the use of OC-1, a new type of CAR T-cell therapy, for patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) or lymphoma (T-LL). The therapy involves modifying a patient’s own T-cells to target CD1a, a protein found on certain cancer cells. This innovative approach aims to provide a potential treatment option for patients who have not responded to standard therapies.

Table of Contents

What is OC-1?

OC-1 is an innovative therapy being studied for the treatment of certain types of blood cancers. Its full name is “AUTOLOGOUS T-CELLS EX VIVO MODIFIED WITH A LENTIVIRAL VECTOR ENCODING A CHIMERIC ANTIGEN RECEPTOR SPECIFIC FOR CD1A,” but it’s also known by several other names, including hCD1a-CAR T, humanised CD1a-CAR T, and OC-1[1]. This therapy belongs to a class of treatments called CAR T-cell therapy, which is a type of immunotherapy that uses a patient’s own modified immune cells to fight cancer.

How Does OC-1 Work?

OC-1 works by modifying a patient’s own T-cells (a type of immune cell) outside the body (ex vivo). Here’s a simplified explanation of the process:

  1. T-cells are collected from the patient’s blood.
  2. These cells are then modified in a laboratory using a lentiviral vector (a type of virus used to deliver genetic material).
  3. The modification adds a special receptor called a chimeric antigen receptor (CAR) to the T-cells. This receptor is designed to recognize a specific protein called CD1A, which is found on certain cancer cells.
  4. The modified T-cells are then grown in large numbers in the lab.
  5. Finally, these modified cells are infused back into the patient’s body, where they can recognize and attack cancer cells that have the CD1A protein[1].

Target Conditions

OC-1 is being developed to treat two specific types of blood cancers:

  • T-cell Acute Lymphoblastic Leukemia (T-ALL): This is a type of cancer that affects the T-cells in the blood and bone marrow. It progresses quickly and can be life-threatening if not treated promptly.
  • T-cell Acute Lymphoblastic Lymphoma (T-LL): This is a similar cancer that primarily affects the lymph nodes and other lymphoid tissues[1].

Specifically, OC-1 is being studied for use in patients with relapsed or refractory (R/R) forms of these cancers. This means the cancer has either come back after initial treatment (relapsed) or did not respond well to standard treatments (refractory)[1].

Clinical Trial Details

A clinical trial is currently underway to study OC-1. Here are some key details about the trial:

  • It’s a “first-in-human” study, meaning it’s the first time this therapy is being tested in people.
  • The trial is exploratory, open-label (meaning everyone knows which treatment they’re receiving), and single-arm (all participants receive the same treatment).
  • It’s being conducted at multiple medical centers.
  • The trial uses a dose escalation design, which means different groups of patients will receive different doses of OC-1 to find the safest and most effective dose[1].

Eligibility Criteria

To participate in the OC-1 clinical trial, patients must meet certain criteria. Some key eligibility factors include:

  • Age: Patients must be either children older than 2 years or adults.
  • Cancer type: Patients must have relapsed or refractory T-ALL or T-LL that is CD1a-positive (meaning the cancer cells have the CD1A protein).
  • Previous treatments: Patients must have tried at least two standard therapy lines without success[1].

There are also several exclusion criteria, such as certain organ dysfunctions, uncontrolled infections, or pregnancy, that would prevent a person from participating in the trial[1].

Potential Benefits

While the effectiveness of OC-1 is still being studied, the researchers hope to see several potential benefits, including:

  • Inducing remission (reduction or disappearance of cancer symptoms) in patients who haven’t responded to other treatments.
  • Improving overall survival rates for patients with these difficult-to-treat cancers.
  • Providing a new treatment option for patients who have exhausted other alternatives[1].

Safety Considerations

As with any new treatment, safety is a primary concern in the OC-1 clinical trial. Researchers will be closely monitoring for side effects, including:

  • Cytokine Release Syndrome (CRS): A condition where the immune system becomes overly activated, potentially causing fever, low blood pressure, and other symptoms.
  • Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): A neurological side effect that can occur with some immunotherapies.
  • Other potential side effects on the skin, blood cells, and overall health[1].

It’s important to note that as this is a first-in-human trial, not all potential side effects may be known at this time. Patients in the trial will be closely monitored for any unexpected effects[1].

Aspect Details
Study Type First in humans, exploratory, open-label, single-arm, multicentre, non-competitive, dose escalation
Therapy OC-1 (hCD1a-CAR T cells)
Target Conditions Relapsed/refractory T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (T-LL)
Patient Eligibility Children >2 years and adults with CD1a-positive R/R T-ALL/LL, ≥20% CD1a antigen blast expression
Primary Objectives Assess safety, monitor adverse events, evaluate immune system impact
Secondary Objectives Evaluate treatment response, duration of response, overall survival, OC-1 cell persistence
Dosing Strategy Dose escalation across four cohorts, ranging from 0.5 x10^6 to 5 x10^6 OC-1 cells/kg
Administration Intravenous infusion in multiple fractions
Key Endpoints Adverse events, CRS and ICANS incidence, remission rate, MRD response, progression-free survival

FAQ

  • What is OC-1 therapy? OC-1 is a type of CAR T-cell therapy that uses a patient's own T-cells, which are modified in a laboratory to target CD1a, a protein found on certain cancer cells. This therapy is being studied for patients with relapsed or refractory T-cell acute lymphoblastic leukemia or lymphoma.
  • Who is eligible for this clinical trial? The trial is open to children older than 2 years and adults with relapsed or refractory CD1a-positive T-ALL or T-LL. Patients must have at least 20% CD1a antigen blast expression and have not responded to at least two previous lines of therapy.
  • What are the main objectives of the trial? The primary objective is to assess the safety of OC-1 in patients with relapsed/refractory CD1a-positive T-ALL/LL. Secondary objectives include evaluating the treatment response, duration of response, overall survival, and persistence of OC-1 cells in the blood after administration.
  • How is the OC-1 therapy administered? OC-1 is administered as a suspension for intravenous infusion. The trial uses a dose-escalation approach, with different cohorts receiving varying doses of OC-1 cells, divided into multiple fractions.
  • What are the potential side effects being monitored? The trial is closely monitoring for adverse events, particularly severe cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and treatment-related dermatological events. The study also assesses the impact on the patient's immune system and overall safety profile.

Ongoing Clinical Trials on Autologous T-Cells Ex Vivo Modified With A Lentiviral Vector Encoding A Chimeric Antigen Receptor Specific For Cd1A

  • Long-term Follow-up Study for Patients with Relapsed/Refractory T-cell Acute Lymphoblastic Leukemia/Lymphoma Treated with OC-1 Cells

    Recruiting

    3 1 1
    Investigated drugs:
    Spain

  • Study on the Safety and Effectiveness of OC-1 Therapy for Patients with Relapsed or Refractory T-cell Acute Lymphoblastic Leukemia or Lymphoma

    Recruiting

    1 1 1
    Investigated drugs:
    Spain

Glossary

  • CAR T-cell therapy: A type of treatment that uses a patient's own T-cells (a type of immune cell) that have been genetically modified in the laboratory to better recognize and attack cancer cells.
  • T-cell acute lymphoblastic leukemia (T-ALL): A type of blood cancer that affects T-cells, a specific type of white blood cell. It progresses quickly and affects the bone marrow, blood, and sometimes other organs.
  • Lymphoblastic lymphoma (T-LL): A type of cancer that affects T-cells and is similar to T-ALL but primarily involves lymph nodes and other organs rather than the bone marrow.
  • Relapsed/Refractory (R/R): Refers to cancer that has either returned after a period of improvement (relapsed) or has not responded to previous treatments (refractory).
  • CD1a: A protein found on the surface of certain cells, including some cancer cells, which is targeted by the OC-1 therapy.
  • Cytokine Release Syndrome (CRS): A potential side effect of some immunotherapies, including CAR T-cell therapy, where the immune system becomes overly activated, causing symptoms like fever, low blood pressure, and difficulty breathing.
  • Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): A neurological side effect that can occur with some immunotherapies, causing symptoms such as confusion, difficulty speaking, or seizures.
  • Minimal Residual Disease (MRD): A small number of cancer cells that remain in the body during or after treatment, which can be detected using very sensitive tests.
  • Allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT): A procedure where a patient receives blood-forming stem cells from a genetically similar donor to replace their diseased bone marrow.

References

  1. http://clinicaltrials.eu/trial/study-on-the-safety-and-effectiveness-of-oc-1-therapy-for-patients-with-relapsed-or-refractory-t-cell-acute-lymphoblastic-leukemia-or-lymphoma/