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Bispecific Protein With A High-Affinity T-Cell Receptor Domain Fused To An Antibody Single-Chain Variable Fragment Against Cd3

A groundbreaking clinical trial is underway to evaluate IMC-M113V, a new bispecific protein designed to target chronic HIV infection. This innovative treatment combines a high-affinity T-cell receptor domain with an antibody fragment against CD3, potentially offering a new approach for patients with suppressed viral loads. The study aims to assess the safety, effectiveness, and potential for long-term viral control in HIV-positive individuals who are currently on antiretroviral therapy.

Table of Contents

What is IMC-M113V?

IMC-M113V is a new experimental drug being studied for the treatment of chronic HIV infection[1]. It is classified as a bispecific protein, which means it can bind to two different targets at the same time. Specifically, IMC-M113V consists of two main parts:

  1. A high-affinity T-cell receptor domain
  2. An antibody single-chain variable fragment that targets CD3 (a protein found on T cells)

This unique structure allows IMC-M113V to potentially engage the immune system in a new way to fight HIV infection. The drug is being developed by Immunocore Limited and is currently in clinical trials to evaluate its safety and effectiveness[1].

How Does IMC-M113V Work?

While the exact mechanism of action is still being studied, IMC-M113V is designed to work in a novel way compared to traditional HIV treatments. Here’s a simplified explanation of how it might work:

  1. The T-cell receptor part of IMC-M113V can recognize and bind to HIV-infected cells.
  2. The CD3-targeting part can attach to T cells, which are important immune cells.
  3. By connecting HIV-infected cells with T cells, IMC-M113V may help the immune system better recognize and eliminate HIV-infected cells.

This approach is different from current antiretroviral therapies (ART) that primarily work by preventing the virus from replicating. IMC-M113V aims to harness the body’s own immune system to fight HIV[1].

Clinical Trial Overview

A clinical trial is currently underway to study IMC-M113V in patients with chronic HIV infection. The trial is titled “An open-label dose-escalation study evaluating the safety, pharmacokinetics and antiviral activity of IMC-M113V in HLA-A*2:01 positive subjects with chronic HIV infection who are virologically suppressed.”[1]

The main objectives of this trial are:

  • To evaluate the safety and tolerability of IMC-M113V
  • To study how the drug moves through and is processed by the body (pharmacokinetics)
  • To assess the antiviral activity of IMC-M113V against HIV
  • To determine the best dosing regimen for future studies

Eligibility Criteria

The trial has specific criteria for who can participate. Some key eligibility requirements include[1]:

  • Being HLA-A*02:01-positive (a specific genetic marker)
  • Having HIV-1 infection and being on continuous antiretroviral therapy (ART) for 1-15 years
  • Having an undetectable HIV viral load for at least 12 months
  • Having a CD4+ T cell count above 450 cells/µL

There are also several exclusion criteria, such as having certain medical conditions or recent use of specific medications. It’s important to note that these criteria ensure the safety of participants and the reliability of the study results.

Study Design

The clinical trial is divided into two main parts[1]:

  1. Part 1: Single Ascending Dose (SAD) Study

    In this part, participants receive a single dose of IMC-M113V. The dose is gradually increased in different groups of participants to find a safe and effective dose.

  2. Part 2: Multiple Ascending Dose (MAD) Study

    In this part, participants receive multiple doses of IMC-M113V over 12 weeks. This helps researchers understand the effects of repeated dosing.

Both parts of the study include careful monitoring of participants’ health and HIV status. In Part 2, there’s also a period where participants stop their regular HIV medication to see if IMC-M113V can help control the virus on its own.

Potential Benefits and Risks

As with any experimental treatment, there are potential benefits and risks to participating in this clinical trial[1]:

Potential Benefits:

  • Access to a new, potentially effective HIV treatment
  • Closer monitoring of HIV status and overall health
  • Contributing to the advancement of HIV treatment research

Potential Risks:

  • Unknown side effects of IMC-M113V
  • Possible increase in HIV viral load during treatment interruption (in Part 2)
  • Time commitment and inconvenience of frequent clinic visits

Conclusion

IMC-M113V represents a promising new approach to HIV treatment. By potentially engaging the immune system in a new way, it may offer hope for better control of HIV infection. However, it’s important to remember that this treatment is still in the experimental stage. The ongoing clinical trial will provide crucial information about its safety and effectiveness. If you’re interested in learning more or potentially participating in this or other HIV clinical trials, it’s best to discuss this with your healthcare provider.

Aspect Details
Study Drug IMC-M113V (Bispecific protein with high-affinity T-cell receptor domain fused to antibody fragment against CD3)
Study Type Phase 1/2, open-label, dose-escalation study
Target Population HLA-A*02:01-positive adults with chronic HIV infection, virologically suppressed on ART
Study Structure Part 1: Single Ascending Dose (SAD), Part 2: Multiple Ascending Dose (MAD)
Primary Objectives Evaluate safety, tolerability, and pharmacokinetics of IMC-M113V
Secondary Objectives Assess antiviral activity, immune response changes, and potential for post-treatment control
Key Inclusion Criteria On ART for 1-15 years, undetectable viral load, CD4+ count >450 cells/μL
Key Exclusion Criteria HIV controllers, recent AIDS-defining conditions, significant medical conditions
Treatment Duration Single dose in Part 1, weekly doses up to Week 12 in Part 2
Follow-up Period Up to 36 weeks, including analytical treatment interruption in Part 2

FAQ

  • What is IMC-M113V and how does it work? IMC-M113V is a bispecific protein that combines a high-affinity T-cell receptor domain with an antibody fragment targeting CD3. It's designed to potentially enhance the immune system's ability to fight HIV in patients with chronic infection.
  • Who is eligible to participate in this clinical trial? Eligible participants are HLA-A*02:01-positive adults with chronic HIV infection who have been on continuous antiretroviral therapy for 1-15 years, have undetectable viral loads, and meet specific CD4+ T cell count criteria.
  • What are the main objectives of the study? The study aims to evaluate the safety, tolerability, and pharmacokinetics of IMC-M113V in single and multiple doses. It also seeks to assess the drug's antiviral activity and potential for post-treatment control during a therapy interruption period.
  • How is the study structured? The study is divided into two parts: Part 1 is a Single Ascending Dose (SAD) study, and Part 2 is a Multiple Ascending Dose (MAD) study. Both parts involve careful monitoring of participants' responses to the treatment.
  • What potential benefits could this treatment offer? If successful, IMC-M113V could potentially provide a new treatment option for people with chronic HIV infection, possibly leading to better viral control or even periods of treatment-free remission. However, it's important to note that the study is still in early phases, and more research is needed to confirm its effectiveness and safety.

Ongoing Clinical Trials on Bispecific Protein With A High-Affinity T-Cell Receptor Domain Fused To An Antibody Single-Chain Variable Fragment Against Cd3

  • Study of IMC-M113V for Patients with Chronic HIV Infection Who Are Virologically Suppressed

    Recruiting

    2 1 1
    Investigated diseases:
    Investigated drugs:
    Belgium Spain

Glossary

  • Bispecific Protein: A type of engineered protein that can bind to two different targets simultaneously, in this case, combining a T-cell receptor domain with an antibody fragment against CD3.
  • HLA-A*02:01: A specific type of Human Leukocyte Antigen (HLA) gene, which is important in the immune system's ability to recognize and respond to infections.
  • Antiretroviral Therapy (ART): A combination of medications used to treat HIV infection by suppressing the virus and slowing the progression of the disease.
  • CD4+ T cell count: A measure of the number of CD4 T lymphocytes (white blood cells) in the blood, which is an important indicator of immune system health in HIV patients.
  • Viral Load: The amount of HIV genetic material (RNA) in a blood sample, reported as copies per milliliter. An 'undetectable' viral load means the level of HIV in the blood is too low to be detected by standard tests.
  • Pharmacokinetics (PK): The study of how a drug moves through the body, including its absorption, distribution, metabolism, and excretion.
  • Pharmacodynamics (PD): The study of the biochemical and physiological effects of drugs on the body, including their mechanisms of action and relationship between drug concentration and effect.
  • Dose-Limiting Toxicity (DLT): Side effects of a drug that are severe enough to prevent an increase in dose or require a dose reduction in a clinical trial.
  • Analytical Therapy Interruption: A planned pause in antiretroviral therapy under close medical supervision to assess the effects of an experimental treatment on HIV control.
  • Post-Treatment Control: The ability to maintain low levels of HIV without antiretroviral therapy after receiving a specific treatment.

References

  1. http://clinicaltrials.eu/trial/study-of-imc-m113v-for-patients-with-chronic-hiv-infection-who-are-virologically-suppressed/