Immunotherapy Strategies: Monoclonal Antibodies

Overview of Immunotherapy

• Immunotherapy is a treatment that modulates the immune system to fight disease.
• It harnesses the body’s own immune system to target and destroy pathogens, cancer cells, or reduce autoimmune responses.
• Unlike traditional therapies like chemotherapy, immunotherapy aims to enhance or suppress the immune response specifically.

KEY TAKEAWAY: Immunotherapy uses the body’s own immune system to fight disease, either by enhancing or suppressing the immune response.

Monoclonal Antibodies (mAbs)

What are Monoclonal Antibodies?

• Monoclonal antibodies (mAbs) are antibodies produced by identical immune cells that are clones of a single parent cell.
• They are designed to bind to a specific antigen.
• MAbs can be produced in large quantities in vitro.

Production of Monoclonal Antibodies

1. Antigen Injection: An animal (typically a mouse) is injected with a specific antigen.
2. Immune Response: The mouse’s immune system responds by producing plasma cells that secrete antibodies specific to the antigen.
3. Spleen Cell Extraction: Spleen cells (containing the antibody-producing plasma cells) are extracted from the mouse.
4. Fusion with Myeloma Cells: The spleen cells are fused with myeloma cells (cancerous plasma cells) to create hybridoma cells. Myeloma cells are used because they are immortal and can divide indefinitely.
5. Selection of Hybridoma Cells: The hybridoma cells are cultured in a selective medium (e.g., HAT medium) that allows only the hybridoma cells to survive. Unfused spleen cells die because they have a limited lifespan, and unfused myeloma cells die because they lack a specific enzyme.
6. Cloning and Screening: Hybridoma cells are cloned, and each clone is screened to identify those producing the desired antibody.
7. Mass Production: The selected hybridoma clones are cultured to produce large quantities of the monoclonal antibody.

Diagram Description

The diagram shows the process of creating monoclonal antibodies:
1. A mouse is injected with antigen X.
2. Mouse spleen cells are extracted and some of these cells make antibodies to antigen X.
3. These spleen cells are mixed and fused with mutant mouse myeloma cells that can’t grow in HAT medium.
4. The fused cells are transferred to HAT medium, where unfused cells die and fused cells grow.
5. Single cells are cultured in separate wells.
6. Each well is tested for antibody to antigen X.

REMEMBER: Hybridoma cells = antibody-producing plasma cell + myeloma cell. HAT medium selects for hybridomas.

Properties of Monoclonal Antibodies

VCAA FOCUS: Understand the steps involved in creating monoclonal antibodies and the purpose of each step.

Immunotherapy for Autoimmune Diseases

Autoimmune Diseases: An Overview

• Autoimmune diseases occur when the immune system mistakenly attacks the body’s own tissues and organs.
• Examples include rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus.

Monoclonal Antibodies in Autoimmune Disease Treatment

• MAbs can be designed to suppress the immune response in autoimmune diseases.
• They can target specific immune cells (e.g., T cells or B cells) or cytokines involved in the autoimmune response.
• Mechanisms of action:
  • Depletion of Immune Cells: Some mAbs can bind to and eliminate specific immune cells, such as B cells (e.g., Rituximab in rheumatoid arthritis).
  • Blocking Cytokine Activity: Other mAbs can block the activity of pro-inflammatory cytokines (e.g., TNF-α inhibitors like Infliximab in rheumatoid arthritis).
  • Interfering with Immune Cell Activation: MAbs can interfere with the activation of immune cells by blocking co-stimulatory molecules.

Examples of mAbs used in Autoimmune Diseases

EXAM TIP: Be able to explain how monoclonal antibodies can be used to suppress the immune response in autoimmune diseases, contrasting this with their use to enhance the immune response in cancer.

Immunotherapy for Cancer

Cancer: An Overview

• Cancer is characterized by uncontrolled cell growth and the ability of these cells to invade other parts of the body.
• Cancer cells often have unique antigens on their surface that can be targeted by the immune system.

Monoclonal Antibodies in Cancer Treatment

• MAbs can be designed to enhance the immune response against cancer cells.
• Mechanisms of action:
  • Direct Cell Killing: Some mAbs can bind to cancer cells and directly induce cell death (apoptosis).
  • Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC): MAbs can bind to cancer cells and recruit immune cells (e.g., NK cells) to destroy the cancer cells.
  • Complement-Dependent Cytotoxicity (CDC): MAbs can activate the complement system, leading to the destruction of cancer cells.
  • Blocking Growth Signals: Some mAbs can block growth factor receptors on cancer cells, preventing them from receiving signals that promote growth and proliferation.
  • Targeted Delivery of Chemotherapy or Radioisotopes: MAbs can be conjugated (linked) to chemotherapy drugs or radioisotopes to deliver these toxic substances directly to cancer cells.

Examples of mAbs used in Cancer Treatment

COMMON MISTAKE: Confusing the mechanisms of action of different monoclonal antibodies. Understand how each MAb specifically targets cancer cells or modulates the immune system.

Antibody-Drug Conjugates (ADCs)

• Antibody-drug conjugates (ADCs) are monoclonal antibodies linked to a cytotoxic drug.
• The antibody targets the cancer cell, and the drug kills it.
• This approach reduces systemic toxicity because the drug is delivered specifically to cancer cells.

APPLICATION: The development of monoclonal antibodies has revolutionized the treatment of cancer and autoimmune diseases, offering more targeted and effective therapies with fewer side effects compared to traditional treatments.

Combining mAbs with Other Therapies

• Monoclonal antibodies are often used in combination with other therapies, such as chemotherapy, radiation therapy, or surgery.
• This approach can improve treatment outcomes by targeting cancer cells through multiple mechanisms.

STUDY HINT: Create a table comparing and contrasting the use of monoclonal antibodies in treating autoimmune diseases and cancer, focusing on the differences in their mechanisms of action and the goals of treatment.