Definition
- CTLA-4 inhibitors are immune checkpoint inhibitors that block CTLA-4, a negative regulator of T-cell activation.
- Blocking CTLA-4 enhances T-cell activation and proliferation, improving antitumor immune response.
Key Approved Drug
Mechanism of Action
- CTLA-4 normally inhibits T-cell activation by competing with CD28 for binding to B7 on antigen-presenting cells.
- Ipilimumab blocks CTLA-4, allowing CD28 to bind B7 → enhanced T-cell activation and proliferation.
- Increases antitumor immune response, leading to tumor cell killing.
Toxicities (Immune-Related Adverse Events)
- Gastrointestinal: colitis, diarrhea, abdominal pain
- Hepatic: hepatitis (elevated AST/ALT, bilirubin)
- Endocrine: hypophysitis, thyroiditis, adrenal insufficiency
- Dermatologic: rash, pruritus, vitiligo
- Pulmonary: pneumonitis (less common)
- Other: infusion reactions, fatigue, rare neurologic events
Management:
- Most irAEs are immune-mediated and may require corticosteroids or other immunosuppressants.
- Early recognition is critical to prevent severe complications.
Monitoring
- Baseline labs: CBC, CMP, thyroid function tests, adrenal function
- Monitor symptoms of colitis, hepatitis, pneumonitis, or endocrinopathy during and after treatment
- Educate patients to report new symptoms immediately
Summary
CTLA-4 inhibitors like ipilimumab enhance T-cell–mediated antitumor immunity. They are effective in melanoma and certain solid tumors but carry a high risk of immune-related adverse events, requiring vigilant monitoring and early management.
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