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Tesnatilimab Biosimilar: Advancing CD38-Targeted Therapy

Tesnatilimab Biosimilar: Advancing CD38-Targeted Therapy

Tesnatilimab is a monoclonal antibody targeting CD38, a transmembrane glycoprotein highly expressed on malignant plasma cells in multiple myeloma (MM) and other hematologic malignancies. By engaging immune mechanisms such as antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), Tesnatilimab enhances tumor cell destruction. The biosimilar provides a cost-effective, accessible alternative, broadening the reach of this life-saving treatment.


This article delves into the mechanism of action, clinical applications, and advantages of Tesnatilimab biosimilar in modern oncology.


1. Understanding CD38 and Its Role in Cancer

What is CD38?


CD38 is a glycoprotein involved in:


  • Signal Transduction: Regulating calcium signaling and cell adhesion.
  • Immune Suppression: Contributing to an immunosuppressive tumor microenvironment.
  • Overexpression in Malignancies: Highly expressed on malignant plasma cells in MM and in some lymphomas and leukemias.

Why Target CD38?


CD38 is a tumor-specific marker in MM and other hematologic cancers, making it an effective target for monoclonal antibody therapy.


2. Tesnatilimab Biosimilar: A Cost-Effective Solution 

Features of the Biosimilar


Tesnatilimab biosimilar mirrors the original monoclonal antibody in efficacy and safety while being more affordable.


  • Target: CD38 on malignant plasma cells.
  • Mechanism: Triggers immune-mediated tumor cell destruction and reduces immunosuppression.
  • Affordability: Expands access to advanced therapies, particularly in resource-limited settings.

3. Mechanism of Action 

Step
Details
CD38 Binding
The biosimilar binds to CD38 on malignant plasma cells, marking them for immune destruction.
Immune Activation
Triggers ADCC and CDC, enhancing immune-mediated tumor cell killing.
Modulation of Tregs
Reduces immunosuppressive regulatory T cells (Tregs), reactivating effector T-cell responses.
Tumor Microenvironment
Reprograms the tumor microenvironment, enhancing overall anti-tumor immunity.

4. Clinical Applications 

Multiple Myeloma (MM)



Frontline Therapy


  • Used in combination with proteasome inhibitors (e.g., bortezomib) or immunomodulatory drugs (e.g., lenalidomide).
  • Improves response rates and progression-free survival in newly diagnosed MM.

Relapsed or Refractory MM


  • Effective as monotherapy or in combination regimens for patients with relapsed or refractory MM.

Other Hematologic Malignancies



Chronic Lymphocytic Leukemia (CLL)


  • Investigated for its potential in targeting CD38-positive CLL cells.

Lymphomas


  • Effective in subsets of non-Hodgkin lymphoma with CD38 expression.

5. Benefits of Tesnatilimab Biosimilar 

Tumor-Specific Activity


Selective binding to CD38 ensures targeted tumor cell destruction while sparing healthy tissues.



Enhanced Immune Activation


By reducing immunosuppressive cells, Tesnatilimab biosimilar enhances the activity of effector T cells and NK cells.



Cost-Effective Access


The biosimilar lowers the financial burden of CD38-targeted therapy, increasing global accessibility.


6. Challenges and Considerations

Adverse Effects


  • Infusion Reactions: Common but manageable with premedication.
  • Hematologic Toxicity: Neutropenia and thrombocytopenia require monitoring and supportive care.

Resistance Mechanisms


  • Tumor cells may downregulate CD38 or upregulate compensatory pathways, necessitating combination therapy.

7. Comparison: Tesnatilimab vs. Biosimilar 

Feature
Tesnatilimab
Biosimilar
Target
CD38 on malignant plasma cells.

CD38 on malignant plasma cells.

Mechanism

Engages ADCC, CDC, and modulates the tumor microenvironment.

Engages ADCC, CDC, and modulates the tumor microenvironment.
Indications
MM, CLL, and CD38-positive lymphomas.
MM, CLL, and CD38-positive lymphomas.
Efficacy
Proven in clinical trials.
Equivalent in preclinical and clinical studies.
Cost
High  
Reduced, improving accessibility.


8. Future Directions

Expanded Indications


  • Investigating the biosimilar in solid tumors with CD38 expression.
  • Evaluating its use in pediatric hematologic malignancies.

Combination Therapies


  • Checkpoint Inhibitors: Combining with PD-1/PD-L1 inhibitors for enhanced anti-tumor efficacy.
  • CAR-T Cells: Exploring synergies with CD38-directed CAR-T therapies.

9. Summary Table 

Aspect
Details
Target
CD38, overexpressed in multiple myeloma and other hematologic malignancies.
Primary Use
Treating MM, CLL, and CD38-positive lymphomas.
Mechanism of Action
Triggers immune-mediated cytotoxicity and reduces immunosuppressive cells.
Biosimilar Benefits
Affordable, accessible, and clinically equivalent to Tesnatilimab.


Conclusion 

The Tesnatilimab biosimilar represents a significant advancement in CD38-targeted therapy. By combining tumor-specific activity with immune modulation, it offers effective treatment for multiple myeloma and other hematologic cancers. As a cost-effective alternative, the biosimilar broadens access to innovative therapies, improving outcomes for patients worldwide.


References 

  1. Mateos, M.V., et al., 2020. Targeting CD38 in multiple myeloma: Clinical updates on monoclonal antibodies. Leukemia, 34(4), pp.984-997.
  2. ClinicalTrials.gov, 2023. Studies on Tesnatilimab and biosimilar therapies. Available at www.clinicaltrials.gov. 
  3. European Medicines Agency (EMA), 2023. Guidelines for biosimilar development in hematologic malignancies. Available at www.ema.europa.eu. 
  4. van de Donk, N.W.C.J., et al., 2016. CD38 as a therapeutic target in hematologic malignancies. Immunology Reviews, 270(1), pp.95-112.
  5. Chiu, H., et al., 2021. Overcoming resistance in CD38-targeted therapies: New strategies and combinations. Blood Advances, 5(6), pp.2453-2463.

10th Dec 2024 Shanza Riaz

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