Tumor-associated glycoprotein 72

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]

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 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:

• Tumor Progression: TAG-72 forms part of the mucinous barrier that shields tumor cells from immune recognition.^[12]
• Cell Adhesion and Metastasis: Its Glycosylation influences how tumor cells interact with the extracellular matrix, facilitating metastasis.^[13]

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.^[9]

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:

• Cancer diagnosis and staging^[20]
• Monitoring recurrence and therapy effectiveness
• Targeted Cancer Therapies^[9]

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

• Monoclonal Antibody Therapy:
  • Minretumomab (CC49) has been studied for targeting TAG-72 in solid tumors.^[21]
  • Anatumomab mafenatox is an anti-TAG-72 antibody conjugated with toxins for cancer treatment.^[22]
• CAR-T Cell Therapy: CAR-T cells engineered to recognize TAG-72 have been tested in ovarian and colorectal cancer.^[23]

Cancer association

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

Gastrointestinal

• Colorectal cancer: TAG-72 is overexpressed in colorectal Adenocarcinoma, and serum levels often reflect tumor stage and prognosis^[24]
• Gastric cancer: CA 72-4, an immunoassay detecting TAG-72, is widely used for diagnosing and monitoring gastric cancer.^[25]
• Pancreatic cancer: TAG-72 levels have helped in diagnosing late stage pancreatic cancers.^[26]

Gynecological

• Ovarian cancer: TAG-72 expression correlates with tumor stage and patient prognosis.^[27]

Other cancers

• Lung cancer: TAG-72 is present in a subset of non-small cell lung carcinomas.^[28]
• Breast cancer: Although less specific, TAG-72 has been detected in certain aggressive breast cancer subtypes.^[29]