Alemtuzumab (CAMPATH 1H) Induction Therapy in Cadaveric Kidney Transplantation―Efficacy and Safety at Five Years

Watson, Christopher J.; Bradley, J. Andrew; Friend, Peter J.; Firth, John D.; Taylor, Craig; Bradley, John R.; Smith, Kenneth G. C.; Thiru, S; Jamieson, Neville V.; Hale, Geoff; Waldmann, Herman; Calne, R. Y.

doi:10.1111/j.1600-6143.2005.00822.x

Cited by 216 publications

(128 citation statements)

References 25 publications

Supporting

Mentioning

114

Contrasting

Unclassified

Order By: Relevance

“…ponents of the immune system or target cell surface adhesion molecules (34). One mAb of particular interest is anti-leukocyte function associated antigen-1 (antiThe success of the Edmonton Protocol has placed islet transplantation in the spotlight as a viable alternative LFA-1), which binds to LFA-1 (CD11a/CD18), a member of a family of structurally and functionally similar for the treatment of type 1 diabetes mellitus (T1DM), a chronic metabolic disorder characterized by the autoimleukocyte differentiation antigens that is involved in the homing, adhesion, and activation of lymphocytes (18, mune destruction of the insulin-producing β-cells of the pancreas (27).…”

Section: Introductionmentioning

confidence: 99%

Monotherapy with Anti-LFA-1 Monoclonal Antibody Promotes Long-Term Survival of Rat Islet Xenografts

et al. 2008

View full text Add to dashboard Cite

Previously we demonstrated that anti-LFA-1 monoclonal (mAb) could promote long-term survival of discordant porcine islet xenografts in mice. The aim of this study, therefore, was to determine whether a shortterm administration of anti-LFA-1 mAb would promote long-term survival of concordant rat islet xenografts in mice, and whether combining short-term administration of anti-LFA-1 mAb therapy with an immunosuppressive drug, rapamycin, would facilitate islet xenograft survival. Streptozotocin-induced diabetic BALB/c mice were transplanted with 500 Wistar-Furth rat islets under the kidney capsule and were either left untreated or treated with short-term administration of rapamycin (0.2 mg/kg) alone, anti-LFA-1 mAb (0.2 mg/ dose) alone, or a combination of rapamycin and anti-LFA-1 mAb using the same doses. All untreated mice rejected their grafts by 24 days posttransplantation with a mean graft survival time of 18.8 ± 2.5 days posttransplantation (n = 5). All mice treated with rapamycin alone had prolonged islet graft survival but eventually rejected their islet grafts by 81 days posttransplantation. In contrast, the majority of the mice (27/ 28) treated with anti-LFA-1 mAb alone maintained long-term normoglycemia (>100 days). Rapamycin in combination with anti-LFA-1 mAb proved equally effective with 29 of 30 mice maintaining normoglycemia for more than 100 days posttransplantation. Low levels of mouse anti-rat antibodies, as well as a decrease in the degree of mononuclear cell infiltration of the islet graft, closely correlated with long-term islet xenograft survival. These results demonstrate that monotherapy with anti-LFA-1 mAb is highly effective in promoting long-term survival of rat islet xenografts and that combination of anti-LFA-1 mAb with rapamycin does not facilitate nor abrogate the induction of long-term xenograft survival by anti-LFA-1 mAb therapy in BALB/c mice. Our study indicates that immunomodulation through mAb therapy could form a significant component of future antirejection therapies in clinical islet xenotransplantation.

show abstract

Section: Introductionmentioning

confidence: 99%

Monotherapy with Anti-LFA-1 Monoclonal Antibody Promotes Long-Term Survival of Rat Islet Xenografts

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Although data on the association between alemtuzumab induction and PTLD in kidney transplant recipients are limited, there seems to be no association. 39,40 This was confirmed in a UNOS registry study comparing no induction, depleting and non-depleting induction therapy. 31 Based on decreased acute rejection rates anti-interleukin-2 receptor (CD25) monoclonal antibodies have emerged as an important part of immunosuppressive regimens in kidney transplant recipients due to selective depletion of activated T cells.…”

Section: Monoclonal T Cell Depleting and Non-depleting Antibodiesmentioning

confidence: 61%

Posttransplant Lymphoproliferative Disorders Following Kidney Transplantation

Dierickx¹

2011

After the Kidney Transplant - The Patients and Their Allograft

View full text Add to dashboard Cite

“…Monoclonal antibodies (mAb) directed against T cell or its subset surface proteins, including the T-cell receptor and costimulatory molecules, have proven to be effective immunosuppressive agents (1)(2)(3)(4)(5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Anti-CD45RB Monoclonal Antibody Prolongs Renal Allograft Survival in Cynomolgus Monkeys

Chen

Luke

Yang

et al. 2007

American Journal of Transplantation

View full text Add to dashboard Cite

Previously, an anti-CD45RB monoclonal antibody (mAb) has been shown to induce murine allograft tolerance. The present study was performed to assess the ability of an anti-human CD45RB mAb to prevent rejection in a monkey MHC-mismatched kidney transplant model. The recipients were allocated into the following treatment groups: (1) isotype control IgG; (2) mouse anti-human CD45RB IgG1 (6G3); (3) human-mouse chimeric anti-CD45RB-IgG1 (C6G3-IgG1); (4) human-mouse chimeric anti-CD45RB-IgG2 (C6G3-IgG2); (5) tacrolimus at a subtherapeutic dose and (6) tacrolimus and C6G3-IgG1 in combination. Monotherapy with anti-CD45RB mAb significantly prolonged renal allograft survival to a median survival of 21 days. Adding a subtherapeutic dose of tacrolimus improved the efficacy of the anti-CD45RB mAb, achieving a median survival of 85 days, whereas a subtherapeutic dose of tacrolimus alone only moderately prolonged survival to 27 days. Treatment with anti-CD45RB mAb resulted in an alteration of the CD45RB hi : CD45RB lo cell ratio in the peripheral blood. We have, for the first time, demonstrated that an anti-human CD45RB mAb (6G3) can prolong graft survival. Induction with an anti-CD45RB mAb improves the efficacy of tacrolimus in the prevention of rejection. These encouraging results indicate that an anti-CD45RB mAb may be valuable in future clinical transplantation.

show abstract

Alemtuzumab (CAMPATH 1H) Induction Therapy in Cadaveric Kidney Transplantation―Efficacy and Safety at Five Years

Cited by 216 publications

References 25 publications

Monotherapy with Anti-LFA-1 Monoclonal Antibody Promotes Long-Term Survival of Rat Islet Xenografts

Monotherapy with Anti-LFA-1 Monoclonal Antibody Promotes Long-Term Survival of Rat Islet Xenografts

Posttransplant Lymphoproliferative Disorders Following Kidney Transplantation

Anti-CD45RB Monoclonal Antibody Prolongs Renal Allograft Survival in Cynomolgus Monkeys

Contact Info

Product

Resources

About