Pancarcinoma T/Tn Antigen Detects Human Carcinoma Long before Biopsy Does and Its Vaccine Prevents Breast Carcinoma Recurrencea

Springer, Georg F.; Desai, Pankaja; Tegtmeyer, H.; Spencer, Bruce D.; Scanlon, Edward F.

doi:10.1111/j.1749-6632.1993.tb44029.x

Cited by 37 publications

(18 citation statements)

References 7 publications

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“…Patients with breast cancer were administered typhoid vaccine, which elicits anti-Tn antigens due the presence of the Tn-like antigens on Salmonella typhi. Anti-tumor efficacy was evaluated and some positive results were observed [198]. More recent studies in this direction have explored specific defined synthetic conjugates [175] containing glycopeptides with one or more GalNAc α 1-O-Ser/Thr modifications [199–201].…”

Section: Targeting the Tn Antigen In Cancermentioning

confidence: 99%

The Cosmc connection to the Tn antigen in cancer

Aryal

Kudelka

et al. 2014

CBM

122

125

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The Tn antigen is a tumor-associated carbohydrate antigen that is not normally expressed in peripheral tissues or blood cells. Expression of this antigen, which is found in a majority of human carcinomas of all types, arises from a blockage in the normal O-glycosylation pathway in which glycans are extended from the common precursor GalNAcα1-O-Ser/Thr (Tn antigen). This precursor is generated in the Golgi apparatus on newly synthesized glycoproteins by a family of polypeptide αN-acetylgalactosaminyltransferases (ppGalNAcTs) and then extended to the common core 1 O-glycan Galβ1-3GalNAcα1-O-Ser/Thr (T antigen) by a single enzyme termed the T-synthase (core 1 β3-galactosyltransferase or C1GalT). Formation of the active form of the T-synthase requires a unique molecular chaperone termed Cosmc, encoded by Cosmc on the X-chromosome (Xq24 in humans, Xc3 in mice). Cosmc resides in the endoplasmic reticulum (ER) and prevents misfolding, aggregation, and proteasome-dependent degradation of newly synthesized T-synthase. Loss of expression of active T-synthase or Cosmc can lead to expression of the Tn antigen, along with its sialylated version Sialyl Tn antigen as observed in several cancers. Both genetic and epigenetic pathways, in addition to potential metabolic regulation, can result in abnormal expression of the Tn antigen. Engineered expression of the Tn antigen by disruption of either C1GalT (T-syn) or Cosmc in mice is associated with a tremendous range of pathologies and engineered expression of the Tn antigen in mouse embryos leads to embryonic death. Studies indicate that many membrane glycoproteins expressing the Tn antigen and/or truncated O-glycans may be dysfunctional, due to degradation and/or misfolding. Thus, expression of normal O-glycans is associated with health and homeostasis whereas truncation of O-glycans, e.g. the Tn and/or Sialyl Tn antigens is associated with cancer and other pathologies.

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Section: Targeting the Tn Antigen In Cancermentioning

confidence: 99%

The Cosmc connection to the Tn antigen in cancer

Aryal

Kudelka

et al. 2014

CBM

122

125

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“…They found that a microbial contaminant, later attributed to neuraminidase, results in cold agglutination of RBCs when mixed with serum due to normal anti-T antibodies. Georg Springer first identified T as a pan-carcinoma antigen, along with his studies of Tn in the 1970s (Springer, 1984; Springer et al, 1975, 1980; Springer, Desai, Tegtmeyer, Spencer, & Scanlon, 1993). …”

Section: Altered O-glycan Structures Observed In Cancermentioning

confidence: 99%

Simple Sugars to Complex Disease—Mucin-Type O-Glycans in Cancer

Kudelka¹,

Ju²,

Heimburg-Molinaro³

et al. 2015

Advances in Cancer Research

202

192

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Mucin-type O-glycans are a class of glycans initiated with N-acetylgalactosamine (GalNAc) α-linked primarily to Ser/Thr residues within glycoproteins and often extended or branched by sugars or saccharides. Most secretory and membrane-bound proteins receive this modification, which is important in regulating many biological processes. Alterations in mucin-type O-glycans have been described across tumor types and include expression of relatively small-sized, truncated O-glycans and altered terminal structures, both of which are associated with patient prognosis. New discoveries in the identity and expression of tumor-associated O-glycans are providing new avenues for tumor detection and treatment. This chapter describes mucin-type O-glycan biosynthesis, altered mucin-type O-glycans in primary tumors, including mechanisms for structural changes and contributions to the tumor phenotype, and clinical approaches to detect and target altered O-glycans for cancer treatment and management.

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“…Early pioneering work by Springer and colleagues reported experiments for long-term anti-carcinoma vaccination and treatment of breast cancer [84] without delivering additional proof. Tn expression has been linked to tumor progression and targeted cancer treatment which has been used for anti-cancer vaccination and treatment of breast cancer [64].…”

Section: Tac In Gynecological Cancersmentioning

confidence: 99%

Tumor-Associated Glycans and Their Role in Gynecological Cancers: Accelerating Translational Research by Novel High-Throughput Approaches

et al. 2012

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Glycans are important partners in many biological processes, including carcinogenesis. The rapidly developing field of functional glycomics becomes one of the frontiers of biology and biomedicine. Aberrant glycosylation of proteins and lipids occurs commonly during malignant transformation and leads to the expression of specific tumor-associated glycans. The appearance of aberrant glycans on carcinoma cells is typically associated with grade, invasion, metastasis and overall poor prognosis. Cancer-associated carbohydrates are mostly located on the surface of cancer cells and are therefore potential diagnostic biomarkers. Currently, there is increasing interest in cancer-associated aberrant glycosylation, with growing numbers of characteristic cancer targets being detected every day. Breast and ovarian cancer are the most common and lethal malignancies in women, respectively, and potential glycan biomarkers hold promise for early detection and targeted therapies. However, the acceleration of research and comprehensive multi-target investigation of cancer-specific glycans could only be successfully achieved with the help of a combination of novel high-throughput glycomic approaches.

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Pancarcinoma T/Tn Antigen Detects Human Carcinoma Long before Biopsy Does and Its Vaccine Prevents Breast Carcinoma Recurrencea

Cited by 37 publications

References 7 publications

The Cosmc connection to the Tn antigen in cancer

The Cosmc connection to the Tn antigen in cancer

Simple Sugars to Complex Disease—Mucin-Type O-Glycans in Cancer

Tumor-Associated Glycans and Their Role in Gynecological Cancers: Accelerating Translational Research by Novel High-Throughput Approaches

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