Figure 1. Current formats of monospecific IgG used to elicit direct targeting and/or receptor agonism.

Target cell killing (red) and/or receptor agonism (blue) can be evoked using various isotype and formats of mAb; clockwise from top centre illustrating wild-type hIgG1 and mIgG2a as powerful native isotypes capable of delivering direct cell killing. Afucosylation can augment this activity through enhanced affinity to FcγRIII or mFcγRIV, respectively as can amino-acid modifications in the Fc(61), where additional FcγRs can be engaged more effectively. Native hIgG2 can evoke FcγR-independent agonism, via IgG2B forms, which can also be generated through C-S hinge mutations resulting in “locked” IgG2B forms. Reduced affinity mAb in mIgG1 and hIgG2 isotypes can also elicit higher agonism, which can be similarly achieved through interaction with FcγRIIB, again through modifications to the Fc. Finally, Fc-null mutants can be generated through Fc mutations and/or deglycosylation which can allow mAb to deliver their activities (e.g. receptor blocking or agonism) independently of FcγR interaction.