Provided are a set of fully human TSH
receptor (TSHR)-blocking
monoclonal antibodies targeting a CHK36 homolog cluster, a preparation method therefor, and an application thereof. The method comprises the following steps: using
flow cytometry to sort
plasma cells and single memory B cells that specifically recognize TSHR in
peripheral blood of a patient with a
high titer of TSH-blocking antibodies (TBAb), performing
in vitro cloning of
antibody light and heavy chains and performing
recombinant expression, and using hTSHR-CHO cells to perform screening and validation of
antibody properties to obtain a blocking
monoclonal antibody that specifically targets human TSHR. The fully human TSH
receptor-blocking
monoclonal antibodies specifically bind to a TSHR, and effectively block
signal transduction after a TSH binds to a
receptor, inhibit the synthetic
secretion of
thyroid hormones, and significantly reduce and inhibit TSHR expression and
fibrosis in orbital fibroblasts of
effector cells associated with
thyroid-related ocular diseases. The fully human TSH receptor-blocking monoclonal antibodies have broad application prospects in the treatment of Graves'
disease (GD) and other diseases caused by hyperthyroidism, such as
thyroid eye disease (TED).