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CD154 Blockade and Donor-Specific Transfusions in DLA-Identical Marrow Transplantation in Dogs Conditioned with 1 Gy Total Body Irradiation

Identifieur interne : 000536 ( Pmc/Corpus ); précédent : 000535; suivant : 000537

CD154 Blockade and Donor-Specific Transfusions in DLA-Identical Marrow Transplantation in Dogs Conditioned with 1 Gy Total Body Irradiation

Auteurs : Christoph Jochum ; Mechthild Beste ; Eustacia Zellmer ; Scott S. Graves ; Rainer Storb

Source :

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation [ 1083-8791 ] ; 2007.

RBID : PMC:1831459

Abstract

Stable mixed donor/host chimerism has been reliably established in dogs given a sublethal dose of 2 Gy total body irradiation (TBI) before and immunosuppression with mycophenolate mofetil (MMF) or rapamycin combined with cyclosporine (CSP) after marrow transplantation from DLA-identical littermates (HCT). When TBI was reduced to 1 Gy, only transient engraftment was observed. Here we asked whether stable engraftment after 1 Gy TBI could be accomplished by reducing host vs. donor immune responsiveness through preceding CD154 blockade and infusion of donor peripheral blood mononuclear cells (PBMC). The anti-human CD154 antibody, 5c8, cross-reacted with canine lymphocytes and blocked allo-immune responses in vitro. Based on pharmacokinetic studies, six dogs received a single i.v. injection of 5 mg/kg anti-CD154 antibody (day -5) followed one day later by donor PBMC. On day 0, dogs were given 1 Gy TBI and DLA-identical marrow grafts. Postgrafting immunosuppression consisted of MMF and CSP. All six dogs showed initial engraftment, which was sustained in three of the six for >26 weeks, while three dogs rejected their grafts after 9, 22, and 24 weeks, respectively, and survived with autologous recovery. Graft survival was significantly improved over that among 11 historical controls conditioned with 1 Gy TBI and given either MMF or rapamycin with CSP after HCT, all of which rejected their grafts between 3 and 12 weeks (P = 0.03). Preceding donor PBMC infusion and CD154 blockade improved survival of DLA-identical marrow grafts after 1 Gy TBI.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1831459

DOI: 10.1016/j.bbmt.2006.10.031
PubMed: 17241922
PubMed Central: 1831459

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PMC:1831459

Le document en format XML

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<author><name sortKey="Jochum, Christoph" sort="Jochum, Christoph" uniqKey="Jochum C" first="Christoph" last="Jochum">Christoph Jochum</name>
<affiliation><nlm:aff id="A1">Transplantation Biology Program, Clinical Research Division, Fred Hutchinson Cancer Research Center; 1100 Fairview Avenue N, D1-100, PO Box 19024, Seattle, WA, USA, 98109-1024.</nlm:aff>
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<author><name sortKey="Beste, Mechthild" sort="Beste, Mechthild" uniqKey="Beste M" first="Mechthild" last="Beste">Mechthild Beste</name>
<affiliation><nlm:aff id="A1">Transplantation Biology Program, Clinical Research Division, Fred Hutchinson Cancer Research Center; 1100 Fairview Avenue N, D1-100, PO Box 19024, Seattle, WA, USA, 98109-1024.</nlm:aff>
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<author><name sortKey="Zellmer, Eustacia" sort="Zellmer, Eustacia" uniqKey="Zellmer E" first="Eustacia" last="Zellmer">Eustacia Zellmer</name>
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<author><name sortKey="Graves, Scott S" sort="Graves, Scott S" uniqKey="Graves S" first="Scott S." last="Graves">Scott S. Graves</name>
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<author><name sortKey="Storb, Rainer" sort="Storb, Rainer" uniqKey="Storb R" first="Rainer" last="Storb">Rainer Storb</name>
<affiliation><nlm:aff id="A1">Transplantation Biology Program, Clinical Research Division, Fred Hutchinson Cancer Research Center; 1100 Fairview Avenue N, D1-100, PO Box 19024, Seattle, WA, USA, 98109-1024.</nlm:aff>
</affiliation>
<affiliation><nlm:aff id="A2">Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA, 98195.</nlm:aff>
</affiliation>
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<author><name sortKey="Jochum, Christoph" sort="Jochum, Christoph" uniqKey="Jochum C" first="Christoph" last="Jochum">Christoph Jochum</name>
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<author><name sortKey="Beste, Mechthild" sort="Beste, Mechthild" uniqKey="Beste M" first="Mechthild" last="Beste">Mechthild Beste</name>
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</affiliation>
</author>
<author><name sortKey="Zellmer, Eustacia" sort="Zellmer, Eustacia" uniqKey="Zellmer E" first="Eustacia" last="Zellmer">Eustacia Zellmer</name>
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</affiliation>
</author>
<author><name sortKey="Graves, Scott S" sort="Graves, Scott S" uniqKey="Graves S" first="Scott S." last="Graves">Scott S. Graves</name>
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</affiliation>
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<author><name sortKey="Storb, Rainer" sort="Storb, Rainer" uniqKey="Storb R" first="Rainer" last="Storb">Rainer Storb</name>
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</affiliation>
<affiliation><nlm:aff id="A2">Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA, 98195.</nlm:aff>
</affiliation>
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<series><title level="j">Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation</title>
<idno type="ISSN">1083-8791</idno>
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<front><div type="abstract" xml:lang="en"><p id="P1">Stable mixed donor/host chimerism has been reliably established in dogs given a sublethal dose of 2 Gy total body irradiation (TBI) before and immunosuppression with mycophenolate mofetil (MMF) or rapamycin combined with cyclosporine (CSP) after marrow transplantation from DLA-identical littermates (HCT). When TBI was reduced to 1 Gy, only transient engraftment was observed. Here we asked whether stable engraftment after 1 Gy TBI could be accomplished by reducing host vs. donor immune responsiveness through preceding CD154 blockade and infusion of donor peripheral blood mononuclear cells (PBMC). The anti-human CD154 antibody, 5c8, cross-reacted with canine lymphocytes and blocked allo-immune responses in vitro. Based on pharmacokinetic studies, six dogs received a single i.v. injection of 5 mg/kg anti-CD154 antibody (day -5) followed one day later by donor PBMC. On day 0, dogs were given 1 Gy TBI and DLA-identical marrow grafts. Postgrafting immunosuppression consisted of MMF and CSP. All six dogs showed initial engraftment, which was sustained in three of the six for >26 weeks, while three dogs rejected their grafts after 9, 22, and 24 weeks, respectively, and survived with autologous recovery. Graft survival was significantly improved over that among 11 historical controls conditioned with 1 Gy TBI and given either MMF or rapamycin with CSP after HCT, all of which rejected their grafts between 3 and 12 weeks (<italic>P</italic>
 = 0.03). Preceding donor PBMC infusion and CD154 blockade improved survival of DLA-identical marrow grafts after 1 Gy TBI.</p>
</div>
</front>
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<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
  <pmc-dir>properties manuscript</pmc-dir>
  <front><journal-meta><journal-id journal-id-type="nlm-journal-id">9600628</journal-id>
<journal-id journal-id-type="pubmed-jr-id">20830</journal-id>
<journal-id journal-id-type="nlm-ta">Biol Blood Marrow Transplant</journal-id>
<journal-title>Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation</journal-title>
<issn pub-type="ppub">1083-8791</issn>
<issn pub-type="epub">1523-6536</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">17241922</article-id>
<article-id pub-id-type="pmc">1831459</article-id>
<article-id pub-id-type="doi">10.1016/j.bbmt.2006.10.031</article-id>
<article-id pub-id-type="manuscript">NIHMS17433</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>CD154 Blockade and Donor-Specific Transfusions in DLA-Identical Marrow Transplantation in Dogs Conditioned with 1 Gy Total Body Irradiation</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Jochum</surname>
<given-names>Christoph</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Beste</surname>
<given-names>Mechthild</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zellmer</surname>
<given-names>Eustacia</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Graves</surname>
<given-names>Scott S.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Storb</surname>
<given-names>Rainer</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<aff id="A1"><label>1</label>
Transplantation Biology Program, Clinical Research Division, Fred Hutchinson Cancer Research Center; 1100 Fairview Avenue N, D1-100, PO Box 19024, Seattle, WA, USA, 98109-1024.</aff>
<aff id="A2"><label>2</label>
Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA, 98195.</aff>
</contrib-group>
<author-notes><corresp id="CR1"><bold>Address for Correspondence:</bold>
 Rainer Storb, MD, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, D1-100, PO Box 19024, Seattle, WA 98109-1024. E-mail: <email>rstorb@fhcrc.org</email>
; Phone: 206.667.4409; Fax: 206.667.6124.</corresp>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>6</day>
<month>2</month>
<year>2007</year>
</pub-date>
<pub-date pub-type="ppub"><month>2</month>
<year>2007</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>1</day>
<month>2</month>
<year>2008</year>
</pub-date>
<volume>13</volume>
<issue>2</issue>
<fpage>164</fpage>
<lpage>171</lpage>
<abstract><p id="P1">Stable mixed donor/host chimerism has been reliably established in dogs given a sublethal dose of 2 Gy total body irradiation (TBI) before and immunosuppression with mycophenolate mofetil (MMF) or rapamycin combined with cyclosporine (CSP) after marrow transplantation from DLA-identical littermates (HCT). When TBI was reduced to 1 Gy, only transient engraftment was observed. Here we asked whether stable engraftment after 1 Gy TBI could be accomplished by reducing host vs. donor immune responsiveness through preceding CD154 blockade and infusion of donor peripheral blood mononuclear cells (PBMC). The anti-human CD154 antibody, 5c8, cross-reacted with canine lymphocytes and blocked allo-immune responses in vitro. Based on pharmacokinetic studies, six dogs received a single i.v. injection of 5 mg/kg anti-CD154 antibody (day -5) followed one day later by donor PBMC. On day 0, dogs were given 1 Gy TBI and DLA-identical marrow grafts. Postgrafting immunosuppression consisted of MMF and CSP. All six dogs showed initial engraftment, which was sustained in three of the six for >26 weeks, while three dogs rejected their grafts after 9, 22, and 24 weeks, respectively, and survived with autologous recovery. Graft survival was significantly improved over that among 11 historical controls conditioned with 1 Gy TBI and given either MMF or rapamycin with CSP after HCT, all of which rejected their grafts between 3 and 12 weeks (<italic>P</italic>
 = 0.03). Preceding donor PBMC infusion and CD154 blockade improved survival of DLA-identical marrow grafts after 1 Gy TBI.</p>
</abstract>
<kwd-group><kwd>anti-CD154 antibody</kwd>
<kwd>costimulatory blockade</kwd>
<kwd>marrow transplantation</kwd>
<kwd>dogs</kwd>
<kwd>nonmyeloablative conditioning</kwd>
</kwd-group>
<contract-num rid="AI1">U19 AI067770-02</contract-num>
<contract-num rid="CA1">P30 CA015704-33</contract-num>
<contract-num rid="CA1">P01 CA078902-09</contract-num>
<contract-sponsor id="AI1">National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID</contract-sponsor>
<contract-sponsor id="CA1">National Cancer Institute : NCI</contract-sponsor>
</article-meta>
</front>
</pmc>
</record>

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CD154 Blockade and Donor-Specific Transfusions in DLA-Identical Marrow Transplantation in Dogs Conditioned with 1 Gy Total Body Irradiation

CD154 Blockade and Donor-Specific Transfusions in DLA-Identical Marrow Transplantation in Dogs Conditioned with 1 Gy Total Body Irradiation

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