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4r0l

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Revision as of 20:47, 3 August 2016

Anti-canine CD28 antibody, 1C6, bound canine CD28

Structural highlights

4r0l is a 6 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Related:	4lci
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Publication Abstract from PubMed

BACKGROUND: CD28 signal blockade following T cell receptor activation is under intense investigation as a tolerance-inducing therapy for transplantation. Our goal is to produce a CD28-specific reagent as a therapy for the prevention of graft rejection and graft-versus-host disease in the canine model of allogeneic hematopoietic cell transplantation (HCT). METHODS: We infused a monoclonal mouse anti-canine CD28 antibody (1C6 mAb) into four dogs and a fragment of antigen-binding (1C6 Fab) into two dogs. Pharmacokinetics, pathology, cytokine release, and the crystal structure of 1C6 Fv were evaluated. RESULTS: Within an hour of an IV injection of the 1C6 mAb, the dogs became leukopenic and developed a steroid-refractory cytokine storm. Two of the dogs developed high fevers, one experienced diffuse alveolar hemorrhage, and another developed gastrointestinal hemorrhage. The cytokine storm was characterized by elevated plasma levels of MCP-1, IP-10, IL-10, IL-6, and TNF-alpha. In addition, one dog showed elevated levels of IL-2, IL-8, and IL-18. In contrast, infusion of 1C6 Fab was well tolerated without any side effects. Dry-coating 1C6 mAb onto tissue culture plates induced CD3-independent proliferation and TNF-alpha production. Crystal structure analysis revealed that 1C6 binds to canine CD28 in a manner different than previously reported for conventional agonistic or superagonistic antibodies. CONCLUSIONS: These results indicate that dogs and humans develop a similar cytokine storm following infusion ofanti-CD28 mAb, providing an appropriate large animal for further study. 1C6 Fab warrants evaluation as a tolerance-inducing reagent in the canine model of allogeneic HCT.

Anti-CD28 Antibody-Initiated Cytokine Storm in Canines.,Rosinski SL, Storb R, Strong RK, Sale GE, Stone DM, Gewe MM, Friend DJ, Abrams VK, Randolph-Habecker J, Graves SS Transplant Direct. 2015 Mar;1(2). doi: 10.1097/TXD.0000000000000516. PMID:25988188^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Rosinski SL, Storb R, Strong RK, Sale GE, Stone DM, Gewe MM, Friend DJ, Abrams VK, Randolph-Habecker J, Graves SS. Anti-CD28 Antibody-Initiated Cytokine Storm in Canines. Transplant Direct. 2015 Mar;1(2). doi: 10.1097/TXD.0000000000000516. PMID:25988188 doi:http://dx.doi.org/10.1097/TXD.0000000000000516

1 Structural highlights
2 Publication Abstract from PubMed
3 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4r0l"

@@ Line 1: / Line 1: @@
 ==Anti-canine CD28 antibody, 1C6, bound canine CD28==
 <StructureSection load='4r0l' size='340' side='right' caption='[[4r0l]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lci|4lci]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4r0l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r0l OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4r0l RCSB], [http://www.ebi.ac.uk/pdbsum/4r0l PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4r0l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r0l OCA], [http://pdbe.org/4r0l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4r0l RCSB], [http://www.ebi.ac.uk/pdbsum/4r0l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4r0l ProSAT]</span></td></tr>
 </table>
 <div style="background-color:#fffaf0;">
@@ Line 15: / Line 16: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4r0l" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4r0l

From Proteopedia

Revision as of 20:47, 3 August 2016

Anti-canine CD28 antibody, 1C6, bound canine CD28

Structural highlights

Publication Abstract from PubMed

References

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