Human natural antibodies recognizing glycan galβ1-3glcnac (LeC)

The level of human natural antibodies of immunoglobulin M isotype against LeC in patients with breast cancer is lower than in healthy women. The epitope specificity of these antibodies has been characterized using a printed glycan array and enzyme-linked immunosorbent assay (ELISA), the antibodies being isolated from donors’ blood using LeC-Sepharose (LeC is Galβ1-3GlcNAcβ). The isolated antibodies recognize the disaccharide but do not bind to glycans terminated with LeC, which implies the impossibility of binding to regular glycoproteins of non-malignant cells. The avidity (as dissociation constant value) of antibodies probed with a multivalent disaccharide is 10−9 M; the nanomolar level indicates that the concentration is sufficient for physiological binding to the cognate antigen. Testing of several breast cancer cell lines showed the strongest binding to ZR 75-1. Interestingly, only 7% of the cells were positive in a monolayer with a low density, increasing up to 96% at highest density. The enhanced interaction (instead of the expected inhibition) of antibodies with ZR 75-1 cells in the presence of Galβ1-3GlcNAcβ disaccharide, indicates that the target epitope of anti-LeC antibodies is a molecular pattern with a carbohydrate constituent rather than a glycan. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Dobrochaeva K.1 , Khasbiullina N.2, 3, 4 , Shilova N.1, 2, 3 , Antipova N. 1, 5, 6 , Obukhova P.1, 3 , Galanina O.1 , Gorbach M.1 , Popova I.1 , Khaidukov S. 1 , Grishchenko N.7 , Tupitsyn N.7 , Pendu J.L.8 , Bovin N.1, 9
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  • 1 Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 16/10 Miklukho-Maklaya, Moscow, 117997, Russian Federation
  • 2 Semiotik LLC, 16/10 Miklukho-Maklaya, Moscow, 117997, Russian Federation
  • 3 National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov of the Ministry of Healthcare of Russian Federation, 4 Oparin str, Moscow, 117997, Russian Federation
  • 4 N.D.Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky pr, Moscow, 119991, Russian Federation
  • 5 Peoples’Friendship, University of Russia (RUDN), 6 Miklukho-Maklaya, Moscow, 117198, Russian Federation
  • 6 National Research University Higher School of Economics, Moscow, 101000, Russian Federation
  • 7 N.N.Blokhin Russian Cancer Research Centre оf the Ministry of Healthcare of Russian Federation, 24 Kashyrskoe Sh., Moscow, 115478, Russian Federation
  • 8 CRCINA, INSERM, Université d’Angers, Université de Nantes, 8 quai Moncousu, Nantes, 70721-44007, France
  • 9 Centre for Kode Technology Innovation, Auckland University of Technology, 55 Wellesley Street East, Auckland, 1010, New Zealand
Ключевые слова
Breast cancer; Cancer-associated antibodies; LeC antigen; Natural anti-glycan antibodies; Printed glycan array
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Zyryanov S.K., Fitilev S.B., Vozzhaev A.V., Shkrebniova I.I., Klyuev D.A.
Research Results in Pharmacology. Федеральное государственное автономное образовательное учреждение высшего образования "Белгородский государственный национальный исследовательский университет". Том 6. 2020. С. 15-20