Tumor-associated glycoprotein 72

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Tumor-associated glycoprotein 72 (TAG-72) is a glycoprotein that appears on the surface of many cancer cells, including those from the ovary, [1] [2] [3] breast, colon, [4] lung, and pancreatic cancers. [5] [6] TAG-72 is a mucin-like molecule with a molar mass of over 1000 kDa, and is classified as a tumor-associated glycoprotein. [7]

Contents

Discovery

Researchers identified Tumor-associated glycoprotein 72 (TAG-72) in the mid-1980s during the development of the Monoclonal antibody B72.3. These antibodies selectively bound to a high-molecular-weight glycoprotein found on various Carcinoma cells. Later studies confirmed TAG-72 as a Mucin-like molecule with significant Glycosylation, which adds to its high molecular weight. [8] This discovery has supported advancements in cancer diagnostics and therapeutics, especially those targeting TAG-72-expressing tumors. [9]

Structure

TAG-72.png

TAG-72 is a high-molecular-weight glycoprotein(>1,000 Kda), primarily expressed on the surface of various Adenocarcinomas. Its structure is features extensive O-linked glycosylation, [9] which gives it a mucin-like configuration. [9] [10] [8] The glycosylation patterns of TAG-72 include tumor-associated carbohydrate antigens such assialyl-Tn (STn) and Thomsen–Friedenreich antigens, which are contribute to tumor progression and metastasis. [11] These carbohydrate epitopes serve as binding sites for monoclonal antibodies like B72.3 and CC49, enabling targeted cancer detection and treatment. [9]

Pathogenic mechanism

TAG-72 rarely appears in normal adult tissues but is highly present in malignant epithelial cells, which makes it a Tumor-specific antigen. [8] It plays a role in:

Clinical applications

1. Tumor Marker (CA 72-4 Assay)

There was a significant difference (p = 0.005) in the proportion surviving between those patients with no residual TAG-72-positive tissue at the end of surgery (red dashed line) as compared to those patients where residual TAG-72-positive tissue (blue dashed line) remained at the end of surgery. Patient prognosis based on TAG-72 presence after cancer removal surgery.jpg
There was a significant difference (p = 0.005) in the proportion surviving between those patients with no residual TAG-72-positive tissue at the end of surgery (red dashed line) as compared to those patients where residual TAG-72-positive tissue (blue dashed line) remained at the end of surgery.

TAG-72 is commonly measured with radioimmunoassays like CA 72-4, [14] which uses the monoclonal antibodies indium (111In) satumomab pendetide and iodine (125I) minretumomab. [15] [16] [17] [18] [19] This assay has a good specificity for gastric cancer, with a correlation to the neoplasia's extension. It is used for:

Since TAG-72 is tumor-specific, it is a promising target for immunotherapy and antibody-drug conjugates:

Cancer association

TAG-72 is mainly found in epithelial-derived malignancies, including:

Gastrointestinal

Gynecological

Other cancers

References

  1. Ponnusamy MP, Venkatraman G, Singh AP, Chauhan SC, Johansson SL, Jain M, et al. (2007-06-28). "Expression of TAG-72 in ovarian cancer and its correlation with tumor stage and patient prognosis". Cancer Letters. 251 (2): 247–257. doi:10.1016/j.canlet.2006.11.025. PMID   17210225.
  2. Murad JP, Kozlowska AK, Lee HJ, Ramamurthy M, Chang WC, Yazaki P, et al. (2018-11-19). "Effective Targeting of TAG72+ Peritoneal Ovarian Tumors via Regional Delivery of CAR-Engineered T Cells". Frontiers in Immunology. 9: 2268. doi: 10.3389/fimmu.2018.02268 . PMC   6254427 . PMID   30510550.
  3. Shu R, Evtimov VJ, Hammett MV, Nguyen NN, Zhuang J, Hudson PJ, et al. (2021-01-16). "Engineered CAR-T cells targeting TAG-72 and CD47 in ovarian cancer". Molecular Therapy Oncolytics. 20: 325–341. doi:10.1016/j.omto.2021.01.002. PMC   7868933 . PMID   33614914.
  4. Hege KM, Bergsland EK, Fisher GA, Nemunaitis JJ, Warren RS, McArthur JG, et al. (2017-03-21). "Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer". Journal for Immunotherapy of Cancer. 5 22. doi: 10.1186/s40425-017-0222-9 . PMC   5360066 . PMID   28344808.
  5. TAG-72 antigen entry in the public domain NCI Dictionary of Cancer Terms
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PD-icon.svg This article incorporates public domain material from Dictionary of Cancer Terms. U.S. National Cancer Institute.