Immunotherapy - Classes, Mechanisms of Action, Representatives and Common Toxicities
Immunotherapy is a systemic anticancer treatment that enhances the body's immune system to recognize, attack and destroy cancer cells. Unlike chemotherapy, which directly kills tumour cells, immunotherapy stimulates or restores the immune response against malignant cells.
It is used in many malignancies, including:
- Melanoma
- Non- small cell lung cancer
- Renal cell carcinoma
- Bladder cancer
- Head and neck cancer
- Hodgkin lymphoma
- Triple- negative breast cancer
- MSI- high colorectal cancer
Mechanism of Action
Normally, the immune system recognizes and destroys abnormal cells. However, tumour cells develop mechanisms to evade immune detection by activating immune checkpoint pathways, which suppress T- cell activity.
Immunotherapy works by:
- Blocking immune checkpoint proteins.
- Reactivating cytotoxic T lymphocytes.
- Enhancing immune recognition of tumour cells.
- Promoting destruction of malignant cells.
- Restoring the body's antitumour immune response.
Immune Checkpoint Inhibitors
Immune checkpoints normally prevent excessive immune activation and autoimmunity. Tumours exploit these pathways to escape immune destruction.
Checkpoint inhibitors block these inhibitory pathways, allowing T cells to attack cancer cells.
A. PD- 1 Inhibitors
Mechanism of Action
PD- 1 is a receptor on activated T lymphocytes.
When PD- 1 binds to PD- L1 on tumour cells, T- cell activity is suppressed.
PD-1 inhibitors block this interaction, restoring T-cell function and enhancing tumour cell killing.
Representatives
- Pembrolizumab
- Nivolumab
- Cemiplimab
Indications
- Melanoma
- Non- small cell lung cancer
- Renal cell carcinoma
- Bladder cancer
- Head and neck cancer
- Hodgkin lymphoma
- MSI- high colorectal cancer
Common Toxicities
- Fatigue
- Skin rash
- Diarrhea
- Hepatitis
- Pneumonitis
- Colitis
- Endocrine disorders
B. PD- L1 Inhibitors
Mechanism of Action
These drugs bind directly to PD-L1 on tumour cells, preventing interaction with PD- 1 receptors on T cells.
Representatives
- Atezolizumab
- Durvalumab
- Avelumab
Indications
- Lung cancer
- Bladder cancer
- Triple- negative breast cancer
- Hepatocellular carcinoma
Common Toxicities
- Fatigue
- Skin rash
- Thyroid dysfunction
- Pneumonitis
- Hepatitis
C. CTLA- 4 Inhibitors
Mechanism of Action
CTLA- 4 is another inhibitory receptor on T lymphocytes.
Blocking CTLA-4 enhances early T-cell activation and proliferation, producing a stronger immune response.
Representative
- Ipilimumab
Indications
- Melanoma
- Renal cell carcinoma (combined with nivolumab)
Common Toxicities
- Severe colitis
- Hepatitis
- Hypophysitis
- Skin rash
- Endocrine disorders