Tropomyosin Isoform and Diagnostic and Therapeutic Uses Therefor

Invention Summary:

Tropomyosins are microfilament-associated proteins found in all eukaryotes and have been implicated in autoimmune diseases such as ulcerative colitis. To date, eight different isoforms (hTM1, hTM2, hTM3, hTMsmα, hTM5a, hTM5b, hTM4, and hTM5) have been identified. Although anti-tropomyosin autoantibodies have been detected in the sera of patients with ulcerative colitis, the autoantigen triggering the autoantibody response has not been definitively identified. Previous studies at Rutgers have identified hTM5 as the predominant immunogen in ulcerative colitis patients. Ulcerative colitis is difficult to diagnose because its symptoms are similar to other intestinal disorders. Furthermore, about 5% of patients with ulcerative colitis develop colon cancer. Thus, the identification of the autoantigen(s), in particular, the specific isoform of Tropomysoin and the specific epitope(s) that trigger ulcerative colitis and colon related diseases and dysfunction would be therapeutically beneficial.

A new isoform of tropomyosin, named TC22, that predominates in human colon carcinoma has been identified and completely sequenced. Monoclonal antibodies, TC22-2, TC22-4, TC22-6 and TC22-7, specific for this distinctive protein have been generated. A significantly large percentage (83%) of colon cancer tissues obtained from colon cancer patients showed strong reactivity with TC22-4 monoclonal antibody compared with normal colon epithelial cells or normal colonic mucosa tissue from patients with Crohn’s disease. Further, the amount of the TC22 protein was also elevated in ulcerative colitis tissues. Studies with GFP-TC22 revealed a weak interaction of the TC22 protein with actin filaments. During mitosis, the alignment of mitotic spindle is guided by strength of the actin filament-tropomysoin interaction thereby influencing cellular proliferation. The elevated expression of TC22 isoform in colon cancer cells and its abnormal interaction with actin filaments implicate a role for TC22 protein in cellular proliferation and cancer. Thus, this novel biomarker can be used for screening and detection of patients at risk of developing colon cancer and other colon related diseases, and ulcerative colitis.

 

Market Application:

  • To develop in vitro diagnostics for ulcerative colitis and colon cancer.
  • To develop assays for the screening of novel agents capable of modulating the activity of TC22 for therapeutic applications.
  • For research use to further the scientific advancement in the area of colon cancer and ulcerative colitis.
  • For selecting patients for enrolment in clinical trials.

Advantages:

  • Surgery is the only cure for ulcerative colitis. The availability of a monoclonal antibody enables the design of simple and inexpensive diagnostic tests for the early detection and prevention of colon dysfunction and diseases.
  • Current diagnostic methods involve endoscopic or colonoscopic procedures that are expensive and painful. Patients with inflammatory bowel disease for a prolonged period of time are recommended for colonoscopic identification of precancerous dysplasia.

Intellectual Property & Development Status:

United States patent number US RE43,472 granted on June 12, 2012

 

Additional Data:

  • TC22 clones, GFP-TC22 constructs, and eukaryotic expression systems
  • TC22-2 (IgM), TC22-4 (IgG1), TC22-6 (IgM) and TC22-7 (IgM) monoclonal antibodies
Rutgers ID: S01-08
Category(s):
Life Sciences
Diagnostics
Contact:
Yong Zhang
Licensing Manager
848-932-4523
yong.zhang@rutgers.edu
Inventors:
Kiron Das
Jim Jung-Chin Lin
Keywords:
Antibody
Autoimmune
Biomarkers
Drug Screening
Oncology