Makindo Medical Notes

📖 About Anti-OKT3 Antibodies

• Anti-OKT3 (muromonab-CD3) is a murine monoclonal antibody (IgG2a) directed against the CD3 complex on human T cells.
• It was the first monoclonal antibody approved for human use, primarily in transplant medicine.
• Now largely replaced by newer biologics due to adverse effect profile, but still of historical and teaching importance.

⚙️ Mechanism of Action

• Binds to the CD3 epsilon chain (20 kDa glycoprotein) on the T-cell receptor complex.
• Phase 1: Causes transient T-cell activation → cytokine release (IL-2, TNF-α, IFN-γ) → “cytokine release syndrome.”
• Phase 2: Internalisation of the TCR-CD3 complex → inhibition of T-cell proliferation and differentiation → profound but reversible T-cell depletion in peripheral blood.

🩺 Indications

• Prevention and treatment of acute rejection in solid organ transplantation (kidney, liver, heart).
• Generally reserved for steroid-resistant rejection episodes.

⚠️ Side Effects

• Cytokine Release Syndrome (first dose): Fever, chills, rigors, headache, nausea, myalgia, hypotension, pulmonary oedema.
• Infection risk: CMV, HSV, opportunistic bacterial/fungal infections (highest in first 2–3 weeks).
• Haematological: Lymphopenia, thrombocytopenia.
• Neurological: Rare seizures, aseptic meningitis, encephalopathy.
• Long-term: Risk of post-transplant lymphoproliferative disease (PTLD) and malignancy due to immunosuppression.

🔄 Interactions

• Concurrent use with other potent immunosuppressants (e.g., calcineurin inhibitors, corticosteroids) increases infection and malignancy risk.
• For full interaction details, consult BNF or specialist protocols.

🧪 Monitoring & Supportive Measures

• Give first doses under close hospital supervision (ICU/HDU setting if unstable).
• Premedication with corticosteroids, antihistamines, antipyretics reduces cytokine release reactions.
• Prophylactic antivirals (e.g., ganciclovir) and antifungals often co-prescribed.
• Monitor: vital signs, FBC, renal and liver function, CMV surveillance.

💡 Key point: Muromonab-CD3 (OKT3) was a landmark in transplant immunology, but its use has declined due to severe cytokine release reactions and infection/malignancy risk. It has been largely replaced by newer monoclonal antibodies (e.g., basiliximab, alemtuzumab) with safer profiles.