| First Author | Bulliard Y | Year | 2013 |
| Journal | J Exp Med | Volume | 210 |
| Issue | 9 | Pages | 1685-93 |
| PubMed ID | 23897982 | Mgi Jnum | J:202358 |
| Mgi Id | MGI:5518522 | Doi | 10.1084/jem.20130573 |
| Citation | Bulliard Y, et al. (2013) Activating Fc gamma receptors contribute to the antitumor activities of immunoregulatory receptor-targeting antibodies. J Exp Med 210(9):1685-93 |
| abstractText | Fc gamma receptor (FcgammaR) coengagement can facilitate antibody-mediated receptor activation in target cells. In particular, agonistic antibodies that target tumor necrosis factor receptor (TNFR) family members have shown dependence on expression of the inhibitory FcgammaR, FcgammaRIIB. It remains unclear if engagement of FcgammaRIIB also extends to the activities of antibodies targeting immunoregulatory TNFRs expressed by T cells. We have explored the requirement for activating and inhibitory FcgammaRs for the antitumor effects of antibodies targeting the TNFR glucocorticoid-induced TNFR-related protein (GITR; TNFRSF18; CD357) expressed on activated and regulatory T cells (T reg cells). We found that although FcgammaRIIB was dispensable for the in vivo efficacy of anti-GITR antibodies, in contrast, activating FcgammaRs were essential. Surprisingly, the dependence on activating FcgammaRs extended to an antibody targeting the non-TNFR receptor CTLA-4 (CD152) that acts as a negative regulator of T cell immunity. We define a common mechanism that correlated with tumor efficacy, whereby antibodies that coengaged activating FcgammaRs expressed by tumor-associated leukocytes facilitated the selective elimination of intratumoral T cell populations, particularly T reg cells. These findings may have broad implications for antibody engineering efforts aimed at enhancing the therapeutic activity of immunomodulatory antibodies. |
