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Single domain antibodies targeting cd1d

A single-domain antibody and antibody technology, applied in the direction of antibodies, anti-inflammatory agents, anti-infective drugs, etc., can solve problems such as the limitation of T cell receptor diversity

Active Publication Date: 2018-01-02
LAVA THERAPEUTICS BV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] Type 1 NKT cells, or constant NKT cells, are the best known group of NKT cells and differ from conventional αβ T cells in that their T cell receptors are more restricted in diversity (“constant”)

Method used

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  • Single domain antibodies targeting cd1d
  • Single domain antibodies targeting cd1d
  • Single domain antibodies targeting cd1d

Examples

Experimental program
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Effect test

Embodiment

[0100] immunity

[0101] Two individual llamas (Lama glama) were immunized as described (Roovers RC et al. Cancer Immunol Immunother. 2007;56:303-17). Briefly, 10 8 stable CD1d-transduced C1R cells. To construct the phage display library, 150 ml of blood was collected on day 43.

[0102] Selection of CD1d-specific VHHs

[0103]To construct the phage display library, peripheral blood lymphocytes (PBL) were isolated from the collected 150 ml blood samples. cDNA was prepared from isolated lymphocytes and used as a template to amplify the gene encoding the variable domain of the heavy chain-only antibody. The PCR fragment was ligated into pUR8100 phage vector and transformed into E. coli cells. In this way, two VHH libraries were obtained, which were subsequently expressed on phage and used for screening. For this, phage from both libraries were incubated with CDld-transfected HeLa cells for 2 h at 4 °C. Cells were then washed and bound phage were eluted with 100 mM HCl...

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Abstract

The invention relates to compounds, in particular polypeptides that specifically bind to the non-classical MHC protein CD1d and modulate CD1d-mediated biological functions. The invention in particularrelates to such compounds and polypeptides comprising or consisting of at least one single domain antibody, and wherein at least one single domain antibody specifically binds to CD1d. Also provided is for methods and use employing such compounds, polypeptides and / or single-domain antibodies.

Description

technical field [0001] The present invention relates generally to the field of immunology, and more particularly to the field of single domain antibodies that bind to human CD1d, including antibodies that alter CD1d-mediated biological functions including, for example, CD1d-restricted T Activation of cells, including natural killer T (NKT) cells, and regulation of the function of CDld-expressing cells. For example, there are provided compounds comprising at least one single domain antibody that binds to CDld, uses of such complexes comprising at least one single domain antibody and (pharmaceutical) compositions comprising such complexes. Background technique [0002] CDld is a member of the CD1 (cluster of differentiation 1) family of glycoproteins (including CD1a, CD1b, CD1c, CD1d and CD1e) expressed on the surface of various human cells, including antigen presenting cells (APCs). Human CD1d is encoded by CD1D, also known as R3G1. APCs displaying CDld include Langerhans c...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28C07K16/46C12P21/08C12N15/13
CPCC07K16/2833C07K16/46A61P35/00A61P33/06A61P31/18A61K2039/505C07K2317/75C07K2317/569C07K2317/565A61P1/04A61P1/16A61P11/06A61P17/06A61P21/04A61P29/00A61P37/04A61P9/10A61P37/00C07K2317/31C07K16/2809C07K16/30
Inventor 约翰内斯·耶勒·范德弗利特坦尼亚·丹妮丝·德格鲁伊杰亨德里克·马里纳斯·威廉·费尔霍伊尔蕾妮·科妮莉亚·格拉里达·德布鲁恩罗兰·拉姆里斯
Owner LAVA THERAPEUTICS BV
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