Anti-Thomsen-Friedenreich (T) antibody-based ELISA and its application to human breast carcinoma detection

Desai, Pankaja; Ujjainwala, L.H.; Carlstedt, S.C.; Springer, Georg F.

doi:10.1016/0022-1759(95)00246-4

Cited by 40 publications

(38 citation statements)

References 18 publications

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“…It is not yet clear which role antibodies play in the natural anti-cancer defense system. The level of TF-and Tn antibodies was significantly decreased in the serum of primary (not operated) patients with cancer, including patients with the disease in its early stage [6][7][8][9] . Furthermore, the low level of anti-TF IgG was associated with a lower differentiated carcinoma and advanced gastric cancer that suggests an implication for antibodies in the progression and pathology of the tumor [10] .…”

Section: Introductionmentioning

confidence: 99%

Postoperative change of anti-Thomsen-Friedenreich and Tn IgG level: The follow-up study of gastrointestinal cancer patients

Smorodin¹,

Kurtenkov²,

Sergeyev³

et al. 2008

WJG

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AIM:To study the influence of tumor removal on the serum level of IgG antibodies to tumor-associated Thomsen-Friedenreich (TF), Tn carbohydrate epitopes and xenogeneic αGal, and to elucidate on the change of the level during the follow-up as well as its association with the stage and morphology of the tumor and the values of blood parameters in gastrointestinal cancer. METHODS: Sixty patients with gastric cancer and 34 patients with colorectal cancer in stages Ⅰ-Ⅳ without distant metastases were subjected to followup. The level of antibodies in serum was determined by the enzyme-linked immunosorbent assay (ELISA) using synthetic polyacrylamide (PAA) glycoconjugates. Biochemical and haematological analyses were performed using automated equipment. RESULTS: In gastrointestinal cancer, the TF antibody level was found to have elevated significantly after the removal of G3 tumors as compared with the preoperative level (u = 278.5, P < 0.05). After surgery, the TF and Tn antibody level was elevated in the majority of gastric cancer patients (sign test, 20 vs 8, P < 0.05, and 21 vs 8, P < 0.05, respectively). In gastrointestinal cancer, the elevated postoperative level of TF, Tn and αGal antibodies was noted in most patients with G3 tumors (sign test, 22 vs 5, P < 0.01; 19 vs 6, P < 0.05; 24 vs 8, P < 0.01, respectively), but the elevation was not significant in patients with G1 + G2 resected tumors. The postoperative follow-up showed that the percentage of patients with G3 resected tumors of the digestive tract, who had a mean level of anti-TF IgG above the cutoff value (1.53), was significantly higher than that of patients with G1 + G2 resected tumors (χ 2 = 3.89, all patients; χ 2 = 5.34, patients without regional lymph node metastases; P < 0. No positive delayed-type hypersensitivity reaction in skin test challenges with TF-PAA in any of the fifteen patients, including those with a high level of anti-TF IgG, was observed. CONCLUSION: The surgical operation raises the level of anti-carbohydrate IgG in most patients, especially in those with the G3 tumor of the gastrointestinal tract. The follow-up demonstrates that after surgery the low preoperative level of TF antibodies may be considerably increased in patients with the carcinoma in its early stage but remains low in its terminal stages. The stageand morphology-dependent immunosuppression affects the TF-antibody response and may be one of the reasons for unresponsiveness to the immunization with TF-antigens.

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Section: Introductionmentioning

confidence: 99%

Postoperative change of anti-Thomsen-Friedenreich and Tn IgG level: The follow-up study of gastrointestinal cancer patients

Smorodin¹,

Kurtenkov²,

Sergeyev³

et al. 2008

WJG

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“…To generate the corresponding calibration curves for whole IgG and IgM, suitable dilutions of a standard serum (Dade Behring, Liederbach, Germany; containing 9.760 mg/ml IgG and 0.730 mg/ml IgM) were applied. In the case of TF-specific antibody, we followed the calibration protocol of Desai et al [15]. For this, the antigens (TF·-PAA or aGP) bound to the wells were estimated quantitatively in serial ELISAs.…”

Section: Quantitative Estimation Of Igg Igm and Tf-specific Igmmentioning

confidence: 99%

“…In tumor patients, it has been observed that the level of anti-TF antibodies is depressed, since the tumor cells release TF together with parts of their carrier molecules into the blood. Based on this observation, Desai et al [15] developed a diagnostic serum test for carcinomas which measures the binding of antibodies to asialoglycophorin (aGP) by a quantitative IgM-specific ELISA. However, this test has so far not found widespread application in clinical diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Isolation and Characterization of Thomsen-Friedenreich-Specific Antibodies from Human Serum

Butschak

Karsten²

2002

Tumor Biol

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The Thomsen-Friedenreich (TF) disaccharide, galactose (Gal)β1–3GalNAcα-, is a blood group-related oncofetal antigen with remarkable tumor specificity. Postpartum, carbohydrate structures on the cell walls of the gastrointestinal flora evoke natural antibodies of presumed TF specificity. These antibodies may provide an early barrier against TF-carrying tumor cells. Their possible role, however, has been difficult to assess, since so far only a multivalent immunosorbent, asialoglycophorin (aGP), has been employed for their preparation, and therefore their fine specificities have been only insufficiently defined. We have used a novel immunosorbent consisting of synthetic TFα disaccharides (Galβ1–3GalNAcα-) coupled to polyacrylamide (PAA), which itself was covalently bound to cross-linked sepharose. For specificity analyses, aGP and a panel of PAA-conjugated mono- and oligosaccharides were employed. Binding to the PAA moiety was excluded. The affinity-purified anti-TFα antibodies were of the IgM (≧0.5 mg/100 ml of serum) and IgG (approximately 0.05 mg/100 ml of serum) classes. They did partially cross-react with TFβ, although we detected a second group of anti-TFβ antibodies (both IgM and IgG) which did not cross-react with TFα. The affinity-purified TFα antibodies showed only marginal cross-reactivity with the related antigens lactose, Gal, Tn or the Forssman antigen. Besides TF-specific antibodies, we found antibodies to the carbohydrate antigens Tn, Forssman and β-D-Gal as well as to noncarbohydrate epitopes of glycophorin in human serum.

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“…Springer and colleagues further demonstrated that the majority of adults have circulating IgM autoantibodies against T antigen (149). A quotient developed by this group (Q Me ; calculated as the square of the anti-T antigen IgM concentration divided by the concentration of the total IgM times 100) led to the observation of significantly lower levels in patients with breast, colorectal, gastric and many other carcinomas (148,150). Interestingly, the Q Me provided high specificity to not only differentiate between healthy individuals and cancer patients but also between benign conditions and malignancies (148,150).…”

mentioning

confidence: 99%

“…A quotient developed by this group (Q Me ; calculated as the square of the anti-T antigen IgM concentration divided by the concentration of the total IgM times 100) led to the observation of significantly lower levels in patients with breast, colorectal, gastric and many other carcinomas (148,150). Interestingly, the Q Me provided high specificity to not only differentiate between healthy individuals and cancer patients but also between benign conditions and malignancies (148,150). The passing of Dr. Springer halted the development of the Q Me quotient as a pancancer diagnostic tool for early detection of ovarian and other tumors and a clinical trial involving the repeated administration of a T/Tn antigen vaccine to breast cancer patients.…”

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confidence: 99%

The immunomodulating roles of glycoproteins in epithelial ovarian cancer

Felder¹

2012

Front Biosci

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The complexity of the immune system demands an intricate defense mechanism by tumors. Ovarian and other tumors employ specific glycoproteins and the associated glycan sequences to modulate immune responses. Glycoproteins enable tumor cells that express or secrete these molecules to evade immune cell attack and induce the immune system to promote tumor growth. This review focuses first on the immune environment in ovarian cancer, and the mechanisms of activation and inhibition that immune cells undergo in order to either attack or ignore a target cell. Next we illustrate the immunomodulatory roles of ovarian cancer-associated glycans and glycoproteins in 1. preventing immune synapse formation, 2. serving as ligands of immune cell receptors, 3. scavenging cytokines and chemokines, and 4. participating in the formation of autoantibodies against the tumor. The importance of these immunomodulating strategies from the view points of understanding the tumor immunology of ovarian tumors, potential origin of such mechanisms, and specific strategies to circumvent the glycoconjugate-mediated suppression of immune responses is discussed in this review. KeywordsGlycoproteins; T cells; NK cells; Epithelia Ovarian Cancer; MUC16; Glycodelin; MUC1; Mucins; Immune Synapse; Review INTRODUCTIONOvarian cancer is a highly insidious disease that is usually detected at a very late stage when the possibility of an efficient therapeutic management of the cancer is relatively low (1-3). Therefore, in most women with advanced ovarian cancer the five year survival rate is around 30-55% (4). Specific biomarkers that can detect the cancer at an early stage (when the survival rate after treatment is 80%) are not available (5,6). In women with advanced disease, the standard of care includes an initial surgical debulking of the tumor followed by an intense chemotherapy with platinum or taxol based compounds. Under these treatment conditions the cancer regresses and the low level of the tumor is monitored by measuring the Send correspondence to: Manish S. Patankar, Department of Obstetrics and Gynecology, University of Wisconsin-Madison, 600 Highland Avenue, H4/657 CSC, Madison, patankar@wisc.edu. NIH Public Access Author ManuscriptFront Biosci (Elite Ed). Author manuscript; available in PMC 2015 February 12. Published in final edited form as:Front Biosci (Elite Ed). ; 4: 631-650. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript serum concentration of the biomarker CA125 (7-10). A steady elevation in serum CA125 levels from this nadir is indicative of recurrent disease (10).The progression of ovarian cancer requires the cancer cells to first develop on the surface of the ovary or along the walls of the fallopian tubes and then metastasize to other sites within the peritoneum (11)(12)(13)(14)(15)(16)(17)(18). Starting with the initiation of the cancer to metastasis, the tumor cells encounter distinct immunologic environments and therefore have to adapt at each site to not only overcome immune recognition but al...

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Anti-Thomsen-Friedenreich (T) antibody-based ELISA and its application to human breast carcinoma detection

Cited by 40 publications

References 18 publications

Postoperative change of anti-Thomsen-Friedenreich and Tn IgG level: The follow-up study of gastrointestinal cancer patients

Postoperative change of anti-Thomsen-Friedenreich and Tn IgG level: The follow-up study of gastrointestinal cancer patients

Isolation and Characterization of Thomsen-Friedenreich-Specific Antibodies from Human Serum

The immunomodulating roles of glycoproteins in epithelial ovarian cancer

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