| First Author | Dahan R | Year | 2016 |
| Journal | Cancer Cell | Volume | 29 |
| Issue | 6 | Pages | 820-831 |
| PubMed ID | 27265505 | Mgi Jnum | J:232332 |
| Mgi Id | MGI:5776628 | Doi | 10.1016/j.ccell.2016.05.001 |
| Citation | Dahan R, et al. (2016) Therapeutic Activity of Agonistic, Human Anti-CD40 Monoclonal Antibodies Requires Selective FcgammaR Engagement. Cancer Cell 29(6):820-31 |
| abstractText | While engagement of the inhibitory Fcgamma-receptor (FcgammaR) IIB is an absolute requirement for in vivo antitumor activity of agonistic mouse anti-CD40 monoclonal antibodies (mAbs), a similar requirement for human mAbs has been disputed. By using a mouse model humanized for its FcgammaRs and CD40, we revealed that FcgammaRIIB engagement is essential for the activity of human CD40 mAbs, while engagement of the activating FcgammaRIIA inhibits this activity. By engineering Fc variants with selective enhanced binding to FcgammaRIIB, but not to FcgammaRIIA, significantly improved antitumor immunity was observed. These findings highlight the necessity of optimizing the Fc domain for this class of therapeutic antibodies by using appropriate preclinical models that accurately reflect the unique affinities and cellular expression of human FcgammaR. |
