Anti-CD40 monoclonal antibody synergizes with CTLA4-Ig in promoting long-term graft survival in murine models of transplantation.
J Immunol
; 183(3): 1625-35, 2009 Aug 01.
Article
in En
| MEDLINE
| ID: mdl-19592649
ABSTRACT
Blockade of the CD40/CD154 signaling pathway using anti-CD154 Abs has shown promise in attenuating the alloimmune response and promoting long-term graft survival in murine model systems, although side effects observed in humans have hampered its progression through clinical trials. Appropriately designed anti-CD40 Abs may provide a suitable alternative. We investigated two isoforms of a novel monoclonal rat anti-mouse CD40 Ab (7E1) for characteristics and effects mirroring those of anti-CD154 7E1-G1 (an IgG1 isotype); and 7E1-G2b (an IgG2b isotype). In vitro proliferation assays to measure the agonist properties of the two anti-CD40 Abs revealed similar responses when plate bound. However, when present as a soluble stimulus, 7E1-G1 but not 7E1-G2b led to proliferation. 7E1-G2b was as effective as anti-CD154 when administered in vivo in concert with CTLA4-Ig in promoting both allogeneic bone marrow chimerism and skin graft survival, whereas 7E1-G1 was not. The protection observed with 7E1-G2b was not due to depletion of CD40-bearing APCs. These data suggest that an appropriately designed anti-CD40 Ab can promote graft survival as well as anti-CD154, making 7E1-G2b an attractive substitute in mouse models of costimulation blockade-based tolerance regimens.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transplantation, Homologous
/
Immunoglobulins
/
Antigens, CD
/
CD40 Antigens
/
Graft Survival
/
Antibodies, Monoclonal
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Immunol
Year:
2009
Document type:
Article
Affiliation country:
United States