Alefacept promotes co-stimulation blockade based allograft survival in nonhuman primates

Tim A. Weaver; Ali H. Charafeddine; Avinash Agarwal; Alexandra P. Turner; Maria Russell; Frank V. Leopardi; Robert L. Kampen; Linda Stempora; Mingqing Song; Christian P. Larsen; Allan D. Kirk

doi:10.1038/nm.1993

Alefacept promotes co-stimulation blockade based allograft survival in nonhuman primates

Tim A. Weaver, Ali H. Charafeddine, Avinash Agarwal, Alexandra P. Turner, Maria Russell, Frank V. Leopardi, Robert L. Kampen, Linda Stempora, Mingqing Song, Christian P. Larsen, Allan D. Kirk

Surgery

Research output: Contribution to journal › Article › peer-review

172 Scopus citations

Abstract

Memory T cells promote allograft rejection particularly in co-stimulation blockade-based immunosuppressive regimens. Here we show that the CD2-specific fusion protein alefacept (lymphocyte function-associated antigen-3-Ig; LFA -3-Ig) selectively eliminates memory T cells and, when combined with a co-stimulation blockade-based regimen using cytotoxic T lymphocyte antigen-4 (CTLA-4)-Ig, a CD80- and CD86-specific fusion protein, prevents renal allograft rejection and alloantibody formation in nonhuman primates. These results support the immediate translation of a regimen for the prevention of allograft rejection without the use of calcineurin inhibitors, steroids or pan-T cell depletion.

Original language	English
Pages (from-to)	746-749
Number of pages	4
Journal	Nature Medicine
Volume	15
Issue number	7
DOIs	https://doi.org/10.1038/nm.1993
State	Published - Jul 2009

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@article{d23b27f185f04cdcb467b1cf2c2feb84,

title = "Alefacept promotes co-stimulation blockade based allograft survival in nonhuman primates",

abstract = "Memory T cells promote allograft rejection particularly in co-stimulation blockade-based immunosuppressive regimens. Here we show that the CD2-specific fusion protein alefacept (lymphocyte function-associated antigen-3-Ig; LFA -3-Ig) selectively eliminates memory T cells and, when combined with a co-stimulation blockade-based regimen using cytotoxic T lymphocyte antigen-4 (CTLA-4)-Ig, a CD80- and CD86-specific fusion protein, prevents renal allograft rejection and alloantibody formation in nonhuman primates. These results support the immediate translation of a regimen for the prevention of allograft rejection without the use of calcineurin inhibitors, steroids or pan-T cell depletion.",

author = "Weaver, {Tim A.} and Charafeddine, {Ali H.} and Avinash Agarwal and Turner, {Alexandra P.} and Maria Russell and Leopardi, {Frank V.} and Kampen, {Robert L.} and Linda Stempora and Mingqing Song and Larsen, {Christian P.} and Kirk, {Allan D.}",

note = "Funding Information: This study was funded in part by the Division of Intramural Research, National Institute of Diabetes, Digestive and Kidney Disease, NIH (Z01 DK062007-06). Salary support for T.A.W. was provided by the Howard Hughes Medical Institute through the NIH Research Scholars Program. A.D.K. is supported by the National Institutes of Health (1U01AI079223-01A1), the Georgia Research Alliance and the McKelvey Foundation. We gratefully acknowledge the expert assistance of J. Bacher and the staff of the NIH Veterinary Pathology Department.",

year = "2009",

month = jul,

doi = "10.1038/nm.1993",

language = "English",

volume = "15",

pages = "746--749",

journal = "Nature Medicine",

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T1 - Alefacept promotes co-stimulation blockade based allograft survival in nonhuman primates

AU - Weaver, Tim A.

AU - Charafeddine, Ali H.

AU - Agarwal, Avinash

AU - Turner, Alexandra P.

AU - Russell, Maria

AU - Leopardi, Frank V.

AU - Kampen, Robert L.

AU - Stempora, Linda

AU - Song, Mingqing

AU - Larsen, Christian P.

AU - Kirk, Allan D.

N1 - Funding Information: This study was funded in part by the Division of Intramural Research, National Institute of Diabetes, Digestive and Kidney Disease, NIH (Z01 DK062007-06). Salary support for T.A.W. was provided by the Howard Hughes Medical Institute through the NIH Research Scholars Program. A.D.K. is supported by the National Institutes of Health (1U01AI079223-01A1), the Georgia Research Alliance and the McKelvey Foundation. We gratefully acknowledge the expert assistance of J. Bacher and the staff of the NIH Veterinary Pathology Department.

PY - 2009/7

Y1 - 2009/7

N2 - Memory T cells promote allograft rejection particularly in co-stimulation blockade-based immunosuppressive regimens. Here we show that the CD2-specific fusion protein alefacept (lymphocyte function-associated antigen-3-Ig; LFA -3-Ig) selectively eliminates memory T cells and, when combined with a co-stimulation blockade-based regimen using cytotoxic T lymphocyte antigen-4 (CTLA-4)-Ig, a CD80- and CD86-specific fusion protein, prevents renal allograft rejection and alloantibody formation in nonhuman primates. These results support the immediate translation of a regimen for the prevention of allograft rejection without the use of calcineurin inhibitors, steroids or pan-T cell depletion.

AB - Memory T cells promote allograft rejection particularly in co-stimulation blockade-based immunosuppressive regimens. Here we show that the CD2-specific fusion protein alefacept (lymphocyte function-associated antigen-3-Ig; LFA -3-Ig) selectively eliminates memory T cells and, when combined with a co-stimulation blockade-based regimen using cytotoxic T lymphocyte antigen-4 (CTLA-4)-Ig, a CD80- and CD86-specific fusion protein, prevents renal allograft rejection and alloantibody formation in nonhuman primates. These results support the immediate translation of a regimen for the prevention of allograft rejection without the use of calcineurin inhibitors, steroids or pan-T cell depletion.

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JO - Nature Medicine

JF - Nature Medicine

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Alefacept promotes co-stimulation blockade based allograft survival in nonhuman primates

Abstract

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