Biologic Induction Therapy

In many transplant centers, induction therapy with biologic agents is used to delay the use of the nephrotoxic calcineurin inhibitors or to intensify the initial immunosuppressive therapy in patients at high risk of rejection (i.e., repeat transplants, broadly presensitized patients, African American patients, or pediatric patients). Most of the limitations of murine-based mAbs generally were overcome by the introduction of chimeric or humanized mAbs that lack antigenicity and have prolonged serum half-lives. The anti-interleukin-2 receptor (IL-2R) mAbs—frequently termed anti-CD25—were the first biologics proven to be effective as induction agents.

Biologic agents for induction therapy in the prophylaxis of rejection currently are used in ~70% of de novo transplant patients. Biologics for induction can be divided into two groups: depleting agents and immune modulators. Depleting agents consist of lymphocyte immune globulin, antithy-mocyte globulin, and muromonab-CD3 mAb (the latter also produces immune modulation); their efficacy derives from their ability to deplete the recipient's CD3-positive cells at the time of transplantation and antigen presentation. The second group, the anti-IL-2R mAbs, does not deplete T lymphocytes, but rather block IL-2—mediated T-cell activation by binding to the a chain of IL-2R.

For patients with high levels of anti-HLA antibodies, humoral rejection mediated by B cells can be modified by plasmapheresis, usually given every other day for 4—5 treatments followed by intravenous immunoglobulin to suppress antibody production.

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