Open AccessIdentification of LAG3 high affinity aptamers by HT-SELEX and Conserved Motif Accumulation (CMA)
Author(s) -
Mario Martínez Soldevilla,
Sandra Hervás,
Helena Villanueva,
Teresa Lozano,
Obdulia Rabal,
Julen Oyarzábal,
Juan José Lasarte,
Maurizio Bendandi,
Susana Inogés,
Ascensión LópezDíaz de Cerio,
Fernando Pastor
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0185169
Subject(s) - aptamer , systematic evolution of ligands by exponential enrichment , cancer immunotherapy , biology , immune system , t cell , computational biology , immunotherapy , microbiology and biotechnology , cancer research , immunology , rna , genetics , gene
LAG3 receptor belongs to a family of immune-checkpoints expressed in T lymphocytes and other cells of the immune system. It plays an important role as a rheostat of the immune response. Focus on this receptor as a potential therapeutic target in cancer immunotherapy has been underscored after the success of other immune-checkpoint blockade strategies in clinical trials. LAG3 showcases the interest in the field of autoimmunity as several studies show that LAG3-targeting antibodies can also be used for the treatment of autoimmune diseases. In this work we describe the identification of a high-affinity LAG3 aptamer by High Throughput Sequencing SELEX in combination with a study of potential conserved binding modes according to sequence conservation by using 2D-structure prediction and 3D-RNA modeling using Rosetta. The aptamer with the highest accumulation of these conserved sequence motifs displays the highest affinity to LAG3 recombinant soluble proteins and binds to LAG3-expressing lymphocytes. The aptamer described herein has the potential to be used as a therapeutic agent, as it enhances the threshold of T-cell activation. Nonetheless, in future applications, it could also be engineered for treatment of autoimmune diseases by target depletion of LAG3-effector T lymphocytes.