Molecular evolution of specific human antibody against MUC1 mucin results in improved recognition of the antigen on tumor cells.

• The MUC1 mucin is differentially expressed and glycosylated in cancer tissue as opposed to healthy tissue. Due to these differences, MUC1 is considered a potential biomarker suitable for cancer diagnosis and therapy. In a previous study, the human MUC1-specific antibody 12ESC-6 was able to bind a sequence variant of the tandem repeat of MUC1 that is not recognized by many other MUC1-specific antibodies. It was also found to bind efficiently to MUC1-carrying cells. We have now used 12ESC-6 as starting point for random mutagenesis to isolate variants with improved ability to bind MUC1 in human tumor tissue. The resulting 12ESC-6 variants were shown to recognize not only the naked MUC1 tandem repeat but even more so glycosylated variants thereof, in particular those carrying the GalNAc (Tn) glycoform. Selected variants of 12ESC-6 demonstrated improved staining of MUC1 on cell lines using flow cytometry and improved staining of the antigen in breast tumor tissue by immunohistochemistry. Molecular evolution and specific fine-tuning thus have the potential to improve the performance of antibody specificities targeting tumor-associated epitopes on MUC1 mucin.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

Amino Acid Sequence

Amino Acid Substitution

Animals

Antibodies

genetics

Antibody Specificity

Antigens

analysis

Breast Neoplasms

immunology

pathology

CHO Cells

Cell Line

Tumor

Chromatography

Gel

Cricetinae

Cricetulus

Epitopes

analysis

Evolution

Molecular

Female

Humans

Male

Molecular Sequence Data

Mucin-1

analysis

genetics

immunology

Oligonucleotide Array Sequence Analysis

Peptide Fragments

chemistry

Prostatic Neoplasms

immunology

pathology

Reference Values

Repetitive Sequences

Amino Acid

T-Lymphocytes

immunology

Publikations- och innehållstyp

ref (ämneskategori)

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