Category: Bi-Specific mAbs

I am Taclistamab, designed in the lab,
A mighty bi-specific mAb.
One end binds cancer, holding it tight,
One end finds T-cells to join the fight.
I help the immune system take its aim,
And snipe myeloma, ending its game.

How Taclistamab helps Immune System to fight Myeloma

Teclistamab is a new approach of cancer treatment. It has two targets:

1. CD3 receptor of an immune cell, called T lymphocyte or simply T-cell
2. B-cell maturation antigen (BCMA) receptors on the surface some cancers, particularly myeloma cells (multiple myeloma).

Taclistamab belongs to the broader group of biothechnology drugs, called monoclonal antibodies.

Scientists refer monoclonal antibodies (mAbs), which can bind two targets simultaneously bispecific mAbs.

Being bispecific can significantly boost your therapeutic value:

1. One side of a protein can recognise a cancer
2. Another can attach to T-cell, which fights this type of cancer

When you bridge two cells toghether, T-cell would recognise adversary immediately and release cytotoxic chemicals to destoy cancer. The release of cancer DNA and proteins alerts other nearby cells, guiding them directly to the cancer site.

Talistamab can initiate a strong, self-sustained immune response against multiple myeloma. It makes a drug is crucial for both advanced stage of disease or cases where cancer is resistant to the other more conventional type of treatments.

Multiple myeloma

Your bones has tissue, called “bone marrow”. It is a main factory of all blood cells: red (erythrocytes), white (leucocytes), and platelets (thrombocytes).

Normally, your bone marrow produces 100 billion white blood cells each day to protect the body form intruders. Most of them venture to the blood, lymphoid tissues, and other organs. However, one type never leaves the area – B-cells would mature and turn inot the plasma cells. Plasma cells stay in bone marrow.

Plasma cells are bulky, have a lifespan of 2-3 days, and produce an anourmous number of antibodies. Their main function is to learn about a foe and produce a specific proten to fight it.

Multiple myeloma is a cancer of plasma cells. Unlike their normal counterparts, myeloma cells exhibit several distinct characteristics:

• They aggresively multiply through cell division. As their number and volume increases, the pressure builds inside the tight spaces within the leading to pain,bone destructuion, and fractures.
• They can hijack the supply chain redirecting the blood flow and nutrients to fuel their growth, depriving healthy tissues of the bone marrow. Clinically, it will manifest as an anemia and an immune difficiency.
• They fabricate abnormal antibodies, called M-protein. M-protein is a junk and doesn’t fight infections. Kidneys try to keep up eliminating it, but at certain levels it would turn into the amyloid deposites in various organs, leading to organ failures.

Teclistamab Background

• Teclistamab is a bispecific monoclonal antibody against multiple myeloma.
• It is classified as a bi-specific T-Cell engager (BiTe)
• On October 25, 2022, FDA granted accelerated approval to teclistamab-cqyv 
• It was developed by Janssen Biotech, Inc under the name TECVAYLI^®

Clinical Trials

FDA granted an accelerated approval based on the clinical trial MajesTEC-1 (NCT03145181; NCT04557098), a single-arm, multi-cohort, open-label, multi-center study.

Patients, who had previously received at least four more conventional therapies for myeoloma (and still relapsed) have been given the taclistamab. Among 110 in the treatment group, 61.8% acheived a partial or complete remission.

Mechanism of Action

The drug targets the B-cell maturation antigen (BCMA) on malignant plasma cells and CD3 on T cells.

CD3 is protein specific to normal T-cells. It has three chains with the longest having a similar structure to antibody. Tha’s why CD3 belongs to antibody superfamily.

It triggers an initiall stage of immune reaction, so many scientists consider it “a gas or a brakes” of an immune cascade.

Step 1. Activation of T-Cells

Upon binding to CD3, T-cells undergo activation, leading to several crucial responses:

• Increase in cytokine production, especially interferon-gamma and tumor necrosis factor-alpha.
• Being cytotoxic, different cytokines recruite even more immune cells to the cancer site.

Once several cancer cells are destroyed and their by-products enter the bloodstream, more immune cells get attracted by the myeloma site. Scientists call this phenomena amplification of immune response.

This amplification of the immune response is essential for improving therapeutic outcomes but also reponsible for serous side effects, such as Cytokine release syndrome and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).

Step 2. Binding to the Myeloma Cell

BCMA is a valid theraupeutic target, as health plasma cells do not usually express them, while myeloma cells enjoy this “decorum” on their membraines. BCMA helps cancer cell to survive and proliferate.

The activation and proliferation of T-cells lead to a direct cytotoxic effect on myeloma cells. Once activated, T-cells release perforins and granzymes, inducing apoptosis in targeted cancer cells.

The localized action of teclistamab allows for effective tumor cell elimination while sparing surrounding healthy tissue. This targeted approach maximizes therapeutic benefits and minimizes adverse effects, contributing to an effective treatment for multiple myeloma.

Clinical use of Teclistamab

Teclistamab plays a significant role in treating multiple myeloma, particularly for patients with limited treatment options. This section outlines its place in therapy and the recommended treatment regimen.

Place of Teclistamab in Myeloma Treatment

Teclistamab is indicated for patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy:

• liproteasome inhibitors;
• immunomodulatory agents;
• anti-CD38 therapies.

The drug targets B-cell maturation antigen (BCMA), which is critical myeloma life cycle. Solid results from the clinical trials inspire an optimism among researchers and clinicians, suggesting they may soon have a tool to target resistant cancer — a potential breakthrough.

Treatment Regimen and Dosage

Teclistamab is typically administered via subcutaneous (under the skin) injection. The initial dose is 1500 µg, followed by maintenance doses of 750 µg.

Dosing is conducted every week for the first month and then once every two weeks. It’s essential to monitor for potential adverse effects, which may include cytokine release syndrome (CRS).

Careful patient selection and monitoring can help maximize the benefits of teclistamab while minimizing risks. Regular follow-ups ensure timely management of side effects and dosage adjustments if necessary.

Teclistamab Side Effects

Teclistamab can lead to a variety of side effects. Understanding these effects is crucial for managing them effectively during treatment.

Cytokine Release Syndrome

Cytokine Release Syndrome (CRS) is a common reaction associated with Teclistamab. It occurs when the immune system is activated rapidly upon exposure to the drug.

You may experience symptoms ranging from mild to severe.

Common symptoms include:

• Fever
• Chills
• Nausea
• Fatigue
• Headache

Severe cases can lead to hypotension and difficulty breathing. Monitoring for signs of CRS is essential, particularly in the days following administration.

CRS Symptoms

Symptoms of CRS can manifest quickly, often within hours of treatment. Early recognition is key to managing this reaction.

Mild symptoms may resolve with supportive care.

Severe reactions might require treatment interventions such as corticosteroids or anti-inflammatory medications. If symptoms worsen, it is vital to contact your healthcare provider immediately.

Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)

Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) is another serious potential side effect of Teclistamab. This condition can affect the central nervous system and may occur concurrently with CRS.

Symptoms typically include confusion, difficulty speaking, or seizures. The severity of ICANS can vary, and monitoring is crucial.

If you notice any neurological changes, communicate these to your healthcare team.

Management may involve steroid treatment or close observation depending on severity. Your doctor will determine the best approach based on your specific situation.

Teclistamab and Future of Myeloma Treatment

Teclistamab represents a significant advance in myeloma treatment. It targets both B-cell maturation antigen (BCMA) and CD3, engaging T-cells to attack myeloma cells.

Key Benefits:

• Dual-target mechanism: By targeting BCMA, teclistamab effectively directs the immune response against malignant plasma cells.
• Durable responses: Early studies suggest that this therapy can lead to prolonged remission in patients with previously treated myeloma.

Clinical Trials:

Ongoing trials are investigating teclistamab’s efficacy and safety compared to standard treatments. These studies are crucial for understanding its role in the treatment landscape.

Considerations for Clinicians:

• Combination therapies: Teclistamab may be used in combination with other treatments, enhancing its effectiveness.
• Diverse patient populations: It is being tested across various stages of myeloma, which may broaden its applicability.

Future Implications:

As more data emerges, teclistamab could redefine treatment protocols. Its innovative approach may lead to new standards of care in managing myeloma, offering more avenues for relapsing and resistant cases of this cancer.