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

Publication ,  Journal Article
Kirk, AD; Hale, DA; Mannon, RB; Kleiner, DE; Hoffmann, SC; Kampen, RL; Cendales, LK; Tadaki, DK; Harlan, DM; Swanson, SJ
Published in: Transplantation
July 15, 2003

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: T-cell depletion alone does not induce tolerance in humans. These data underscore a prominent role for early responding monocytes in human allograft rejection.

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Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

July 15, 2003

Volume

76

Issue

1

Start / End Page

120 / 129

Location

United States

Related Subject Headings

  • White People
  • United States
  • Transplantation, Homologous
  • Time Factors
  • T-Lymphocytes
  • Surgery
  • Middle Aged
  • Male
  • Lymphocyte Depletion
  • Lymph Nodes
 

Citation

APA
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Kirk, A. D., Hale, D. A., Mannon, R. B., Kleiner, D. E., Hoffmann, S. C., Kampen, R. L., … Swanson, S. J. (2003). Results from a human renal allograft tolerance trial evaluating the humanized CD52-specific monoclonal antibody alemtuzumab (CAMPATH-1H). Transplantation, 76(1), 120–129. https://doi.org/10.1097/01.TP.0000071362.99021.D9
Kirk, Allan D., Douglas A. Hale, Roslyn B. Mannon, David E. Kleiner, Steven C. Hoffmann, Robert L. Kampen, Linda K. Cendales, Douglas K. Tadaki, David M. Harlan, and S John Swanson. “Results from a human renal allograft tolerance trial evaluating the humanized CD52-specific monoclonal antibody alemtuzumab (CAMPATH-1H).Transplantation 76, no. 1 (July 15, 2003): 120–29. https://doi.org/10.1097/01.TP.0000071362.99021.D9.
Kirk AD, Hale DA, Mannon RB, Kleiner DE, Hoffmann SC, Kampen RL, et al. Results from a human renal allograft tolerance trial evaluating the humanized CD52-specific monoclonal antibody alemtuzumab (CAMPATH-1H). Transplantation. 2003 Jul 15;76(1):120–9.
Kirk, Allan D., et al. “Results from a human renal allograft tolerance trial evaluating the humanized CD52-specific monoclonal antibody alemtuzumab (CAMPATH-1H).Transplantation, vol. 76, no. 1, July 2003, pp. 120–29. Pubmed, doi:10.1097/01.TP.0000071362.99021.D9.
Kirk AD, Hale DA, Mannon RB, Kleiner DE, Hoffmann SC, Kampen RL, Cendales LK, Tadaki DK, Harlan DM, Swanson SJ. Results from a human renal allograft tolerance trial evaluating the humanized CD52-specific monoclonal antibody alemtuzumab (CAMPATH-1H). Transplantation. 2003 Jul 15;76(1):120–129.

Published In

Transplantation

DOI

ISSN

0041-1337

Publication Date

July 15, 2003

Volume

76

Issue

1

Start / End Page

120 / 129

Location

United States

Related Subject Headings

  • White People
  • United States
  • Transplantation, Homologous
  • Time Factors
  • T-Lymphocytes
  • Surgery
  • Middle Aged
  • Male
  • Lymphocyte Depletion
  • Lymph Nodes