Results from a human renal allograft tolerance trial evaluating the humanized CD52-specific monoclonal antibody alemtuzumab (Campath-1H)

• Published in: Transplantation Vol. 76; no. 1; pp. 120 - 129
• Main Authors: KIRK, Allan D, HALE, Douglas A, MANNON, Roslyn B, KLEINER, David E, HOFFMANN, Steven C, KAMPEN, Robert L, CENDALES, Linda K, TADAKI, Douglas K, HARLAN, David M, SWANSON, S. John
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott 15-07-2003
• Subjects: Adult; Alemtuzumab; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm - therapeutic use; Biological and medical sciences; Black or African American; Black People; CD52 antigen; Combined surgery. Multiple transplantations; Female; Follow-Up Studies; Graft Rejection - epidemiology; Graft Survival - drug effects; Graft Survival - immunology; Humans; Immunosuppressive Agents - therapeutic use; Kidney Transplantation - immunology; Lymph Nodes - immunology; Lymphocyte Depletion; Male; Medical sciences; Middle Aged; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; T-Lymphocytes - immunology; Time Factors; Transplantation, Homologous; United States; White People; United States; Antigen; Human; Chemotherapy; Depletion; Treatment; Surgery; T-Lymphocyte; Transplantation; Alemtuzumab; Monoclonal antibody; Homotransplantation; Kidney
• ISSN: 0041-1337; 1534-6080
• DOI: 10.1097/01.tp.0000071362.99021.d9

Profound T-cell depletion before allotransplantation with gradual posttransplant T-cell repopulation induces a state of donor-specific immune hyporesponsiveness or tolerance in some animal models. Alemtuzumab (Campath-1H, Millennium Pharmaceuticals, Cambridge, MA) is a humanized CD52-specific monoclonal antibody that produces profound T-cell depletion in humans and reduces the need for maintenance immunosuppression after renal transplantation. We therefore performed a study to determine if pretransplant T-cell depletion with alemtuzumab would induce tolerance in human renal allografts and to evaluate the nature of the alloimmune response in the setting of T-cell depletion.
Seven nonsensitized recipients of living-donor kidneys were treated perioperatively with alemtuzumab and followed postoperatively without maintenance immunosuppression. Patients were evaluated clinically by peripheral flow cytometry, protocol biopsies evaluated immunohistochemically, and real-time polymerase chain reaction-based transcriptional analysis.
Lymphocyte depletion was profound in the periphery and secondary lymphoid tissues. All patients developed reversible rejection episodes within the first month that were characterized by predominantly monocytic (not lymphocytic) infiltrates with only rare T cells in the peripheral blood or allograft. These episodes were responsive to treatment with steroids or sirolimus or both. After therapy, patients remained rejection-free on reduced immunosuppression, generally monotherapy sirolimus, despite the recovery of lymphocytes to normal levels.
T-cell depletion alone does not induce tolerance in humans. These data underscore a prominent role for early responding monocytes in human allograft rejection.