Genetically engineered IgG1 and nanobody oligomers acquire strong intrinsic CD40 agonism.

ABSTRACT: Most anti-CD40 antibodies show robust agonism only upon binding to FcγR⁺ cells, such as B cells, macrophages, or DCs, but a few anti-CD40 antibodies display also strong intrinsic agonism dependent on the recognized epitope and/or isotype. It is worth mentioning, however, that also the anti-CD40 antibodies with intrinsic agonism can show a further increase in agonistic activity when bound by FcγR-expressing cells. Thus, conventional antibodies appear not to be sufficient to trigger the maximum possible CD40 activation independent from FcγR-binding. We proved here the hypothesis that oligomeric and oligovalent anti-CD40 antibody variants generated by genetic engineering display high intrinsic, thus FcγR-independent, agonistic activity. We generated tetra-, hexa- and dodecavalent v

SUBMITTER: Hesen N 

PROVIDER: S-EPMC10793706 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature