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MONOCLONAL
ANTIBODIES
Muromonab-CD3
| Representative Examples: | Muromonab-CD3 (Orthoclone OKT3®), Interleukin-2 Receptor Antagonist (Basiliximab, Simulect®), Daclizumab (Zenapax®) |
| Clinical Use: | Monoclonal Antibodies are used in early rejection prophylaxis and treatment of rejection. |
| General Mechanism: |
Monoclonal antibodies are antigen-specific immunosuppressants that will reduce immune response to alloantigens of the graft while preserving the response to alloantigens to unrelated antigens. These agents are specific to blocking T-cell activation, resulting in rapid depletion of T cells from the circulation by binding of antibody coated T cells to Fc receptors on phagocytic cells. The most recently FDA approved monoclonal antibodies are the IL-2 receptor antagonists genetically engineered to possess both human and murine antibody sequences. The chimerization of these antibodies is an attempt to decrease the immunogenicity of the agent. Other monoclonal antibody-based drugs are still in clinical trials for FDA approval. |
Muromonab-CD3
| Pharmacological Mechanism: | Muromonab-CD3 is the first type of murine monoclonal antibody directed against the epsilon chain of the CD3 molecule (an integral part of the T Cell Receptor complex) and modulates the receptor and inactivates T-cell function blocking both naïve T cells and CTLs. This results in rapid depletion of T cells from circulation and cytokine release. This antibody is used to treat acute rejection and steroid resistant rejection. Several severe adverse effects as a result of Muromonab-CD3 are thought to be a product of the cytokine release inherent in the mechanism of the agent's efficacy. |
| Side Effects: |
Side effects observed
with Muromonab-CD3 use include:
|
| Representative Dose/Route: | The recommended dose for Muromonab-CD3 is 5 mg IV push once a day for 7-14 days. |
Interleukin-2 Receptor Antagonist (Basiliximab)
| Pharmacological Mechanism: | Basiliximab (Simulect®) is a chimeric (70% human and 30% murine) monoclonal antibody utilized in the prevention of acute organ rejection. This monoclonal antibody has a specificity and high affinity for the a subunit of the interleukin (IL)-2 receptor (IL-2Ra, also known as CD25 or Tac) preventing IL-2 from binding to the receptor on the surface of activated T cells. By acting as an IL-2Ra antagonist, Basiliximab inhibits IL-2-mediated activation and proliferation of T cells, the critical step in the cascade of cellular immune response of allograft rejection. Therefore, Basiliximab has a long half-life of approximately 7-12 days and saturates the IL-2 receptor for up to 59 days. Due to its high percentage of humanization in its antibody sequences the occurrence and acuteness of adverse effects is significantly lower when used with standard immunotherapy. |
| Side Effects: |
Side effects observed
with IN-2 receptor antagonist use include:
*since this immunosuppressant is used in combination with other
therapies, it can be assumed that other side effects exist |
|
Representative Dose/Route: |
The prescribed dose of Basiliximab is 20 mg IV 2 hours prior to transplant and 20 mg 4 days after transplant surgery. This immunosuppressant is given as part of the immunotherapeutic regimen. |
Daclizumab
| Pharmacological Mechanism: | Daclizumab is a similar agent as Basiliximab, but is more humanized IgG monoclonal antibody (90% human and 10% murine). It also binds to and inhibits the a-subunit of IL-2 receptor. Daclizumab has a half-life of about 20 days and saturates the IL-2 receptor for up to 120 days (twice as long as Basiliximab). |
| Side Effects: |
Side effects observed
with IN-2 receptor antagonist use include:
*since this immunosuppressant is used in combination with other
therapies, it can be assumed that other side effects exist |
| Representative Dose/Route: | Daclizumab is given as a part of the immunosuppressant therapy in place. The first dose is 1 mg/kg IVgiven around the surgery and then every 14 days for four more doses. |
Corticosteriods Calcineurine Inhibitors Antiproliferative Agents Monoclonal Antibodies Polyclonal Antibodies
Other References
Side Effects Drug Efficacy