CEA-containing immune complexes in sera of patients with colorectal and breast cancer ? analysis of complexed immunoglobulin classes

Fuchs, Christiane; Krapf, F.; Kern, Peter; Hoferichter, Suse; Jäger, Wolfram; Kalden, J. R.

doi:10.1007/bf00205613

Cited by 25 publications

(9 citation statements)

References 17 publications

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“…Most of these assays have been developed for bacterial, viral or allergen antigens. In a few cases, detection of autoantigens as CIC has been proposed to enhance the sensitivity of cancer detection or prognosis monitoring utilizing prostate-specific antigen (PSA), 6 squamous cell carcinoma antigen, 7 carcinoembryonic antigen 8 and CA-125. 9 Thus, autoantigen-antibody complexes have been shown to be useful disease biomarkers, but progress in the discovery of new CICs has been extremely slow.…”

Section: Introductionmentioning

confidence: 99%

High-Throughput Screening for Native Autoantigen–Autoantibody Complexes Using Antibody Microarrays

Rho

Lampe

2013

J. Proteome Res.

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We report on a novel, high-dimensional method to detect autoantibodies that are complexed with their natural autoantigens. Specifically, autoantibody-autoantigen complexes in serum or plasma are directly incubated onto a high-density antibody microarray. Detection of the bound autoantibody-antigen complex is made via fluorescently labeled anti-human immunoglobulin G or other immunoglobulin isotype secondary antibodies and quantification in a microarray scanner. Uncomplexed antibodies do not interfere with this assay. The whole process is very rapid and applicable for high-throughput screening without the need for production of proteins or immunoglobulin purification from the samples. Using these methods, we found that plasma from healthy individuals contains hundreds of autoantibodies complexed with cellular proteins. Thus, this highly sensitive, multiplex method is capable of discovering new autoantibody-antigen or circulating immune complexes many of which will likely be useful for disease detection and characterization.

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Section: Introductionmentioning

confidence: 99%

High-Throughput Screening for Native Autoantigen–Autoantibody Complexes Using Antibody Microarrays

Rho

Lampe

2013

J. Proteome Res.

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“…Tumor antigens associated with immunoglobulins, mainly IgG, can form circulating immune complexes, and this has been reported for few biomarkers, such as carcinoembryonic antigen (CEA) and TA90 for colon cancer,67,68 and MUC-1 or p53 for breast cancer 69. We have recently reported that alfa-fetoprotein (AFP) and squamous cell carcinoma antigen (SCCA) (for liver cancer) and CEA ( for colorectal cancer) could be detected in the serum of patients with cancer, forming complexes with IgM, opening a new gateway for cancer detection 50–52…”

Section: Discussionmentioning

confidence: 99%

Circulating Natural IgM Antibodies against Angiogenin in the Peripheral Blood Sera of Patients with Osteosarcoma as Candidate Biomarkers and Reporters of Tumorigenesis

Savitskaya¹,

Rico²,

Linares³

et al. 2010

Biomark�Cancer

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Background:Tumor immunology research has led to the identification of a number of tumor-associated self antigens, suggesting that most tumors trigger an immunogenic response, as is the case in osteosarcoma, where the detection of natural serum IgM antibodies might achieve the diagnosis of osteosarcoma. Natural IgM antibodies to tumor-associated proteins may expand the number of available tumor biomarkers for osteosarcoma and may be used together in a serum profile to enhance test sensitivity and specificity. Natural IgM antibodies can be consistently detected in the peripheral blood sera months to years before the tumor is diagnosed clinically. The study of the level of a potential biomarker many months (or years) prior to diagnosis is fundamentally important. Integrated circulating and imaging markers in clinical practice treating osteosarcoma have potential applications for controlling tumor angiogenesis.Objectives:To study the expression of natural IgM antibodies to the tumor antigens of angiogenesis in the peripheral blood sera of osteosarcoma patients and healthy individuals, and to develop serum-based predictive biomarkers.Methods:Peripheral venous blood samples were collected from 117 osteosarcoma patients and 117 patients with other tumors. All diagnosis was histologically confirmed. Staging of patients was performed according to the Enneking Surgical Staging System. The control group consisted of 117 age- and sex- matched healthy individuals. In this study, novel immunoconjugates were designed, synthesized and then used to develop a rapid, specific and sensitive enzyme-linked immunosorbent assay (ELISA) method to detect angiogenin (ANG)–IgM directly in the peripheral blood sera of humans.Results:Serum ANG–IgM levels are significantly higher in osteosarcoma patients than in healthy individuals (P < 0.005). Serum ANG–IgM levels varied widely, but were highly dependent on the concentration of IgM (r = 0.85; P < 0.0005). We found ANG–IgM in the sera of 85% of newly diagnosed osteosarcoma patients and ANG–IgM levels were significantly higher in osteosarcoma patients compared to any other tumors (P < 0.001).Conclusions:These results demonstrated that the combined biomarker ANG–IgM has greater sensitivity and specificity in early diagnosis of osteosarcoma patients than the traditional biomarkers (ANG and vascular endothelial growth factor). Circulating ANG–IgM immune complexes can potentially serve as a biomarker for increased risk of osteosarcoma, because relatively high serum levels were also detected in otherwise healthy individuals with a first degree family history of osteosarcoma and in patients with a diagnosis of benign conditions. Immunological aspects of angiogenesis for managing osteosarcoma will have a practical value in early diagnosis, prognosis and monitoring response to antiangiogenic therapy.

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“…On the other hand, there is no evidence to date on the immunogenicity of CEA. There are no reports in the literature of human T-cell responses to CEA, and there are conflicting reports on whether antibodies to CEA exist or are artifacts [29][30][31][32]. Even if tolerance to CEA does exist, it may be broken by the use of a recombinant CEA vaccinia vaccine (designated rV-CEA).…”

Section: Rationale For Success or Failurementioning

confidence: 99%

Strategies for the development of recombinant vaccines for the immunotherapy of breast cancer

Schlom

Kantor

Abrams

et al. 1996

Breast Cancer Res Tr

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The development of recombinant vaccines for specific immunotherapy of carcinoma represents a novel approach for the treatment of breast cancer and other tumor types. This article reviews the various parameters that should be considered in the development of recombinant vaccines. Several breast cancer associated antigens are also discussed which may provide potential target molecules. The human carcinoembryonic antigen (CEA), which is expressed on approximately 50% of breast cancers, represents one such target for immunotherapy. To enhance the immunogenicity of this antigen, a recombinant CEA-vaccinia vaccine, designated rV-CEA, was produced. To study the effects of this vaccine in an animal model, a murine colon carcinoma cell line was transduced with CEA and transplanted into immunocompetent mice for protection and therapy studies. Pre-clinical toxicity studies were also conducted in non-human primates. The results of these studies showed the rV-CEA vaccine to be immunogenic and safe in both rodents and primates, and to elicit good anti-tumor responses in the rodent model. In a Phase I clinical trial in metastatic breast, lung, and colorectal cancer patients involving three immunizations of rV-CEA, at three dose levels, enhancement of T-cell and antibody responses to vaccinia virus proteins were observed with no toxicity. Specific T-cell responses were studied via stimulation of peripheral blood lymphocytes with specific peptide epitopes from the CEA molecule. These studies demonstrated clear cut differences in establishment of T-cell lines pre- versus post-immunization. The T-cell lines were shown to be CD8+ and/or CD4+/CD8+, to lyse EBV transformed B-cells transduced with the CEA gene, and to lyse CEA positive carcinoma cells in a HLA restricted manner. Thus, in a Phase I clinical trial the rV-CEA vaccine has been shown to stimulate a CTL response specific for CEA defined epitopes in cancer patients.

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CEA-containing immune complexes in sera of patients with colorectal and breast cancer ? analysis of complexed immunoglobulin classes

Cited by 25 publications

References 17 publications

High-Throughput Screening for Native Autoantigen–Autoantibody Complexes Using Antibody Microarrays

High-Throughput Screening for Native Autoantigen–Autoantibody Complexes Using Antibody Microarrays

Circulating Natural IgM Antibodies against Angiogenin in the Peripheral Blood Sera of Patients with Osteosarcoma as Candidate Biomarkers and Reporters of Tumorigenesis

Strategies for the development of recombinant vaccines for the immunotherapy of breast cancer

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