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

Persson, JonasLund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH (författare)

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.

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
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

Bäckström, Malin,1967Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology(Swepub:gu)xbamal (författare)
Johansson, H (författare)
Jirström, KarinLund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)pat-kji (författare)
Hansson, Gunnar C.,1951Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi,Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology(Swepub:gu)xhagun (författare)
Ohlin, MatsLund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH(Swepub:lu)immt-moh (författare)
Institutionen för immunteknologiInstitutioner vid LTH (creator_code:org_t)

Ingår i:Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine: Springer Science and Business Media LLC30:4, s. 221-311423-03801010-4283
Ingår i:Tumor Biology: Springer Science and Business Media LLC30:4, s. 221-311010-4283

Av författaren/redakt...: Persson, Jonas; Bäckström, Malin ...; Johansson, H; Jirström, Karin; Hansson, Gunnar ...; Ohlin, Mats

Om ämnet

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Medicinsk biotek ...; och Medicinsk biotek ...

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.