•Monoclonal
antibodies (mAbs)
that stimulate anticancer immune responses are proving increasingly effective
in cancer treatment, with growing evidence that such responses can be harnessed
to provide durable eradication of tumours.
•This
versatile and patented technology provides the exciting opportunity to engineer
clinical reagents with defined, tuneable
therapeutic activity regardless of FcɣR
expression levels in the local microenvironment.
•Through
a combination of in vitro and in vivo approaches, it has been shown that the
human IgG2 hinge and CH1 domains impart FcɣR-independent
agonistic activity to immunostimulatory
mAbs
that bind to -CD40 and that this might also apply to other specificities.
•Activity
is provided by a structurally constrained isoform of hIgG2 due to its unique
arrangement of disulfide bonds which confers distinct agonistic (or super
agonistic) properties to the mAb.
