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Antitumor activities of agonistic anti-TNFR antibodies require differential Fc?RIIB coengagement in vivo.

ABSTRACT: Agonistic anti-TNF receptor (TNFR) superfamily member antibodies are a class of promising antitumor therapies in active clinical investigation. An unexpected requirement for inhibitory Fc? receptor Fc?RIIB coengagement has recently been described for their in vivo antitumor activities. Although these findings have informed the design of more potent antitumor agonistic, anti-TNFR therapies, the underlying mechanism has remained obscure. Through detailed genetic analysis of strains conditionally deleted for Fc?RIIB on defined cellular populations or mutated in specific signaling components, we now demonstrate that different agonistic anti-TNFR antibodies have specific requirements for Fc?RIIB expression on defined cellular populations and function in trans in the absence of Fc?RIIB signaling components, thus supporting a general mechanism of Fc?RIIB cross-linking in vivo for the activities of these antibodies.

SUBMITTER: Li F

PROVIDER: S-EPMC3845179 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Antitumor activities of agonistic anti-TNFR antibodies require differential FcγRIIB coengagement in vivo.

Li Fubin F Ravetch Jeffrey V JV

Proceedings of the National Academy of Sciences of the United States of America 20131111 48

Agonistic anti-TNF receptor (TNFR) superfamily member antibodies are a class of promising antitumor therapies in active clinical investigation. An unexpected requirement for inhibitory Fcγ receptor FcγRIIB coengagement has recently been described for their in vivo antitumor activities. Although these findings have informed the design of more potent antitumor agonistic, anti-TNFR therapies, the underlying mechanism has remained obscure. Through detailed genetic analysis of strains conditionally d ...[more]

PMID: 24218606

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