| First Author | Li F | Year | 2011 |
| Journal | Science | Volume | 333 |
| Issue | 6045 | Pages | 1030-4 |
| PubMed ID | 21852502 | Mgi Jnum | J:174675 |
| Mgi Id | MGI:5140618 | Doi | 10.1126/science.1206954 |
| Citation | Li F, et al. (2011) Inhibitory Fcgamma receptor engagement drives adjuvant and anti-tumor activities of agonistic CD40 antibodies. Science 333(6045):1030-4 |
| abstractText | CD40, a member of the tumor necrosis factor receptor (TNFR) superfamily, is expressed on antigen-presenting cells (APCs) and is essential for immune activation. Although agonistic CD40 antibodies have been developed for immunotherapy, their clinical efficacy has been limited. We have found that coengagement of the Fc domain of agonistic CD40 monoclonal antibodies (mAbs) with the inhibitory Fcgamma receptor FcgammaRIIB is required for immune activation. Direct comparison of mAbs to CD40 enhanced for activating FcgammaR binding, hence capable of cytotoxicity, or for inhibitory FcgammaRIIB binding, revealed that enhancing FcgammaRIIB binding conferred immunostimulatory activity and considerably greater anti-tumor responses. This unexpected requirement for FcgammaRIIB in enhancing CD40-mediated immune activation has direct implications for the design of agonistic antibodies to TNFR as therapeutics. |
