Monoclonal Antibody that Suppresses Thyrotropin Receptor Constitutive Activity

Tech ID: rap000229

Introduction

Thyroid cancer is a cancer that starts in the thyroid gland. According to the American Cancer Society’s estimates, there were 62,980 new cases and 1,890 deaths from thyroid cancer in the United States in 2014. Current treatment methods are not fully effective. The researchers have developed monoclonal antibodies that suppress thyrotropin receptor constitutive activity and have identified a method of using the antibodies to treat thyroid-related diseases, including differentiated thyroid cancer and rare cases of hyperthyroidism secondary to activating TSH receptor mutations. 

 

Technology Description

• The thyrotropin receptor (TSHR), a member of the G protein-coupled receptor (GPCR) superfamily, is a key regulator of thyroid function. Through the TSHR, the natural ligand, thyrotropin (TSH), and pathological autoantibodies (primarily stimulatory, but occasionally blocking) modify many aspects of thyroid hormone synthesis and secretion. Significant TSHR constitutive activity is a clinically relevant phenomenon in the treatment of thyroid carcinoma. After thyroidectomy, suppression of endogenous TSH secretion is a therapeutic goal to prevent or retard the proliferation or metastasis of residual thyroid carcinoma cells. However, even complete TSH suppression cannot eliminate potentially harmful TSHR activity.

• With the high constitutive activity of TSHR, risks associated with suppressing TSH, and side effects of thyroid cancer and disease treatments, there is a need for an inverse agonist of TSHR and a method to decrease its constitutive activity.

• The researchers made a purified antibody that binds specifically to TSHR and has inverse agonist activity. The antibody has been proved to suppress thyroid function in preclinical studies in a mouse model.

 

Stage of Development

The inventors made a purified antibody that binds specifically to TSHR and has inverse agonist activity on the TSHR. The antibody has been proved to suppress thyroid function in preclinical studies in mouse model. 

 

Applications

The antibody can be further developed to treat differentiated thyroid cancer and rare cases of hyperthyroidism secondary to activating TSH receptor mutations.

 

Intellectual Property

US patent US8350012 granted.

 

Publications

Chen et al. Suppression of Thyrotropin Receptor Constitutive Activity by a Monoclonal Antibody with Inverse Agonist Activity. Endocrinology. 2007, 148 (5): 2375-82 [Link]

Patent Information:
For Information, Contact:
Wenyue Du
Senior Associate - IP Management & Licensing
310-423-2241
wenyue.du@cshs.org
Inventors:
Basil Rapoport
Sandra Mclachlan
ChuN-Rong Chen
Keywords:
Endocrinology
Oncology