11.08 Monoclonal Antibodies (Mabs)

1. Definition

• Monoclonal Antibodies (Mabs) are identical antibodies produced by a single clone of hybridoma cells.
• Each Mab is specific to one unique epitope of an antigen, ensuring precise targeting in various applications.

2. Properties

• Specificity: All Mabs have identical variable regions, allowing them to bind exclusively to a single antigen.
• Uniformity: Being identical, Mabs provide consistent and reproducible results in both diagnostic and therapeutic contexts.

3. Production Process

a. Cell Fusion

• Plasma Cells: Naturally produce specific antibodies but cannot divide.
• Cancer Cells (Myeloma Cells): Capable of indefinite division.
• Fusion: Combining plasma cells with myeloma cells to form hybrid cells.

b. Hybridoma Formation

• Hybridoma Cells: Result from the fusion, possessing both antibody-producing ability and the capacity to divide indefinitely.
• Continuous Production: These cells can perpetually produce the specific Mab.

c. Screening

• Selection: Identifying hybridoma clones that produce the desired Mab.
• Culturing: Expanding the selected hybridomas to produce large quantities of the specific Mab.

4. Applications of Monoclonal Antibodies

a. Diagnostic Uses

1. Blood Clot Detection
   • Target: Fibrin, the main protein in blood clots.
   • Method: Mabs labeled with radioactive markers bind to fibrin in clots.
   • Detection: Gamma-ray cameras locate the radioactive signals, identifying clot locations.
2. Blood and Tissue Typing
   • Usage: Routine tests before blood transfusions and organ transplants.
   • Mechanism: Mabs against specific blood group antigens (e.g., anti-A, anti-B, anti-D) cause agglutination if the corresponding antigen is present, ensuring compatibility and preventing immune reactions.
3. Cancer Detection
   • Function: Mabs bind to unique proteins on cancer cell surfaces.
   • Outcome: Helps in locating and identifying cancerous cells within tissues.
4. Infection Identification
   • Capability: Recognize specific strains of viruses or bacteria.
   • Benefit: Allows for precise diagnosis and targeted treatment strategies.

b. Therapeutic Uses

1. Humanized Monoclonal Antibodies
   • Challenge: Animal-derived Mabs can trigger immune reactions in humans.
   • Solutions:
     • Genetic Modification: Altering antibody genes to produce human-like amino acid sequences.
     • Glycosylation Adjustment: Modifying sugar chains on antibodies to resemble those of human antibodies.
   • Advantage: Reduced immunogenicity, allowing safer and repeated administration in patients.
2. Examples of Therapeutic Mabs
   • Trastuzumab (Herceptin)
     • Target: HER2 receptors on breast cancer cells.
     • Action: Marks cancer cells for destruction by the immune system.
   • Ipilimumab
     • Use: Treats melanoma.
     • Mechanism: Blocks CTLA-4, a protein that suppresses immune responses, thereby sustaining T cell activity against cancer cells.
   • Infliximab
     • Application: Treats rheumatoid arthritis and other autoimmune diseases.
     • Function: Binds to TNF-alpha, an inflammatory cytokine, reducing inflammation and preventing cartilage damage.
   • Rituximab
     • Targets: CD20 on B cells.
     • Purpose: Promotes destruction of B cells, used in treating diseases like leukemia, lymphoma, and multiple sclerosis.

5. Key Terms

• Monoclonal Antibody (Mab): An antibody from a single clone of hybridoma cells, specific to one antigen.
• Hybridoma: A fusion cell derived from a plasma cell and a cancer cell, capable of indefinite division and specific antibody production.
• Humanized Mabs: Mabs genetically modified to resemble human antibodies, minimizing immune responses in patients.

6. Advantages of Using Mabs

a. Precision in Diagnosis

• High Specificity: Mabs’ exclusive binding to antigens allows for accurate identification of diseases, such as determining exact blood types or locating cancer cells.

b. Targeted Cancer Treatment

• Selective Targeting: Mabs specifically attack cancer cells, reducing damage to healthy cells compared to traditional chemotherapy and radiotherapy.
• Fewer Side Effects: Enhanced precision leads to fewer adverse effects, improving patient quality of life.

c. Reduced Immune Reactions

• Humanized Mabs: Engineered to resemble human antibodies, lowering the risk of the patient’s immune system rejecting the treatment.
• Repeated Dosing: Safe for multiple administrations without significant immune responses.

7. Example Questions Analysis

a. Blood Typing with Mabs

• Process: Using anti-A, anti-B, and anti-D Mabs to detect corresponding antigens on red blood cells.
• Outcome: Agglutination indicates the presence of specific antigens, ensuring compatibility in blood transfusions and organ transplants, thereby preventing immune rejection.

b. Benefits of Mabs in Treatment

• Diagnostic Advantages: Rapid and accurate detection is crucial for conditions requiring swift medical intervention.
• Cancer Treatment: Mabs’ ability to selectively target cancer cells minimizes collateral damage to healthy tissues, offering a more effective and safer alternative to conventional therapies.