Nucleic acid aptamers targeting lymphocyte activation gene 3 (lag-3) and uses thereof

Abstract

Nucleic acid aptamers capable of binding to lymphocyte activation gene 3 (LAG-3) and uses thereof for modulating immune responses. Such aptamers may comprise a G-rich motif, for example, GX1GGGX2GGTX3A (SEQ ID No: 1), in which each of X1 and X2 are independently G, C, or absent, and X3 is T or C, or L- (G)n-L', in which n is an integer of 5-9 inclusive, and L and L'are nucleotide segments having complementary sequences. Also provided herein are multimeric nucleic acid aptamers containing a backbone moiety, which comprises a palindromic sequence.

Description

[0001] related application [0002] This application claims the benefit under 35 U.S.C. §119 of U.S. Provisional Application No. 62 / 684,139, filed June 12, 2018, and U.S. Provisional Application No. 62 / 740,751, filed October 3, 2018, each of which is adopted in its entirety by Incorporated herein by reference. Background technique [0003] Activated T cells express a variety of co-inhibitory molecules (termed immune checkpoint molecules) to regulate T cell responses. Exemplary immune checkpoint molecules include programmed cell death protein 1 (PD-1), lymphocyte activation gene 3 (LAG-3), and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). These immune checkpoint molecules play an important role in maintaining immune homeostasis and preventing autoimmunity. [0004] Immune checkpoint molecules are often activated in cancer, leading to suppressed anti-tumor immune responses. Therefore, immune checkpoint inhibitor therapy offers effective long-term treatment for a varie...

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