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The novel panel assay to define tumor-associated antigen-binding antibodies in patients with metastatic melanomas may have diagnostic value

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Abstract

We aim to harness the natural humoral immune response by various technologies to get novel biomarkers. A complex antibody analysis in sera and in the tumor microenvironment leads to reveal tumor-specific antibodies. More strategies were introduced to select the most effective one to identify potential tumor antigen-binding capacity of the host. Epstein–Barr virus transformation and cloning with limiting dilution assay, magnetic cell sorting and antibody phage display with further methodological improvements were used in epithelial and neuroectodermal cancers. Column-purified sera of patient with melanoma were tested by immunofluorescence assay, while sera of further melanoma patients were processed for membrane-binding enzyme-linked immunosorbent assay. Some supernatants of selected B cell clones and purified antibodies showed considerable cancer cell binding capacity by immunofluorescence FACS analysis and confocal laser microscopy. Our native tumor cell membrane preparations helped to test soluble scFv and patients’ sera for tumor binder antibodies. A complex tumor immunological study was introduced for patients with melanoma (ethical permission: ETT TUKEB 16462-02/2010); peripheral blood (n = 57) and surgically removed primary or metastatic tumors (n = 44) were gathered and processed at cellular immunological level. The technological developments proved to be important steps forward to the next antibody profile analyses at DNA sequence level. Cancer cell binding of patient-derived antibodies and natural immunoglobulin preparations of pooled plasma product intravenous immunoglobulins support the importance of natural human antibodies. Important cancer diagnostics and novel anticancer strategies are going to be built on these tools.

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Abbreviations

ATCC:

American Type Cell Collections

EBV:

Epstein–Barr virus

GD3:

Ganglioside 3 type disialylated glycosphingolipids

ELISA:

Enzyme-linked immunosorbent assay

FDA:

Food and Drug Administration

JITC:

Journal for ImmunoTherapy of Cancer

HJLCT:

Harry J Loyd Charitable Trust

HSA:

Human serum albumin

IDC:

Invasive ductal carcinoma of the breast

IF:

Immunofluorescence

IHC:

Immunohistochemistry

alphaIFN:

Interferon alpha

IVIG:

Intracenous immunoglobulin

LDA:

Limiting dilution assay

MACS:

Magnetic cell sorting

MBC:

Medullary breast carcinoma

MTT:

2-(4,5-Dimethyl-2-thiazolyl)-3,5-diphenyl-2H-tetrazolium bromide

ETT-TUKEB:

Ministry of Human Resources in Hungary, Hungarian Medical Research Council

NM:

Nodular melanoma

PFA:

Paraformaldehyde

PBMC:

Peripheral blood mononuclear cells

SSM:

Superficial spreading melanoma

TAA:

Tumor-associated antigen

TIL-B:

Tumor infiltrating B cells

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Acknowledgments

We acknowledge the Harry J. Lloyd Charitable Trust Melanoma Research Award (2010) given to B. Kotlan, previous Fulbright No. 1206103 and OTKA T048933 Grants to B. Kotlan as well as her being supported by the Hungarian Cancer Foundation, Budapest, Hungary and a second Fulbright No. 1214104 Grant 2014.

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Authors and Affiliations

  1. Molecular Immunology and Toxicology, National Institute of Oncology, Budapest, Hungary

    Beatrix Kotlan

  2. Center of Surgical and Molecular Tumorpathology, National Institute of Oncology, Budapest, Hungary

    Beatrix Kotlan, Klara Eles, Szabolcs Horvath & Jozsef Toth

  3. Oncodermatology, National Institute of Oncology, Budapest, Hungary

    Gabriella Liszkay & Timea Balatoni

  4. Zabludowitz Center for Autoimmune Diseases, Sheba Medical Center Affiliated to Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel

    Miri Blank & Yehuda Shoenfeld

  5. Pathogenetics, National Institute of Oncology, Budapest, Hungary

    Orsolya Csuka & Judit Olasz

  6. Oncosurgery, National Institute of Oncology, Budapest, Hungary

    Laszlo Toth

  7. Department of Radiological Diagnostics, National Institute of Oncology, Budapest, Hungary

    Gyorgy Naszados & Maria Godeny

  8. County Hospital Tatabanya, Tatabanya, Hungary

    Balazs Banky

  9. National Institute of Oncology, Budapest, Hungary

    Orsolya Csuka, Maria Godeny & Miklos Kasler

  10. Sidra Medical and Research Centre, Doha, Qatar

    Francesco M. Marincola

Authors
  1. Beatrix Kotlan
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  2. Gabriella Liszkay
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  3. Miri Blank
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  15. Miklos Kasler
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  16. Yehuda Shoenfeld
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Correspondence to Beatrix Kotlan.

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Kotlan, B., Liszkay, G., Blank, M. et al. The novel panel assay to define tumor-associated antigen-binding antibodies in patients with metastatic melanomas may have diagnostic value. Immunol Res 61, 11–23 (2015). https://doi.org/10.1007/s12026-014-8600-6

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  • DOI: https://doi.org/10.1007/s12026-014-8600-6

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