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Humanized antibodies to iNKT

An antibody, human technology, applied in the field of treatment to suppress immune response, treatment to suppress iNKT cell function, can solve problems such as low iNKT cell number, ratio or functional human data

Inactive Publication Date: 2014-07-23
NKT THERAPEUTICS
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Second, most human studies are qualitative only, and few human data exist on the functional consequences of modulating iNKT cell number, ratio, or function
Said application shows, on the other hand, that increased iNKT activity can lead to suppressed immune responses

Method used

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  • Humanized antibodies to iNKT
  • Humanized antibodies to iNKT
  • Humanized antibodies to iNKT

Examples

Experimental program
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Effect test

example 1

[0104] Example 1. Generation of composite humanized antibodies from 6B11 murine antibody.

[0105] Briefly, the heavy and light chain V regions (VH and VK) sequences of the anti-iNKT receptor antibody clone 6B11 have been determined (15). Based on these sequences, Composite Human Antibodies were generated TM (Antitope Ltd, Cambridge, UK). Composite Human Antibodies TM It has a variable region consisting of fragments of human sequences with CDRs identical to the sequence of the mouse antibody clone 6B11. Used to construct Composite Human Antibodies TM Fragments of human V region sequences were obtained from the Unrelated Human Antibody Sequence Database. For potential binding to MHC class II using iTOPE TM Analytical testing of each selected sequence fragment and junctions formed by the ligated fragments, and all final Composite Human Antibody TM Sequence variants designed to avoid T cell epitopes. Generate Composite Human Antibody using synthetic oligonucleotides encodi...

example 2

[0128] Example 2. Characterization of NKTT120

[0129] Binding affinity measurements and functional characterization of NKTT120 were performed using recombinant human invariant TCR and cells, and in vivo function was tested in transgenic mice and cynomolgus monkeys. The data show that NKTT120 is highly selective and specific for the human invariant T cell receptor (iTCR) either in purified soluble form or as a membrane protein on iNKT cells. When bound to iTCRs on cells, NKTT120 mediates depletion of those cells. In terms of Fc function, other studies have shown that NKTT120 binds to human FcγRI, C1q and FcγRIII. Finally, NKTT120-mediated depletion of iNKT cells did not induce cytokine responses in human whole blood samples in vitro or in cynomolgus monkeys.

[0130] NKTT120 binds to Hu-siTCR (human soluble iTCR)

[0131] Binding of NKTT120 and other anti-iNKT TCR mAbs was assessed by ELISA and SPR using recombinant soluble human iTCR (Hu-siTCR). In ELISA using Hu-siTCR, w...

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Abstract

Methods of treatment to suppress an immune response are provided. The method comprises administering to a subject in need of treatment a naked blocking antibody that binds selectively iNKT cells in an amount effective to suppress the subject's iNKT cell function. Compositions comprising, an isolated, humanized antibody that binds selectively iNKT cells are also provided.

Description

[0001] Related applications [0002] This application claims the benefit under 35 U.S.C. §119(e) of U.S. Provisional Application No. 61 / 552,337, filed October 27, 2011, the contents of which are hereby incorporated by reference in their entirety. Background technique [0003] Asthma is a relatively common disease worldwide. In 2009, the Centers for Disease Control estimated the prevalence of asthma in the United States to be 8.2% of the population or 24.6 million people. The worldwide burden of asthma is large, with an estimated incidence of more than 300 million cases, and this number is expected to grow to more than 100 million by 2025. [0004] Asthma is one of the costliest diseases in our country. It is estimated that annual costs in the United States on lost health and productivity attributable to asthma exceed $20 billion. In 2006 and 2007, there were approximately 3500 asthma-related deaths in the United States and more than 250,000 worldwide each year. [0005] A...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395
CPCC07K16/2809A61K2039/505C07K2317/24C07K2317/56C07K2317/73C07K2317/732C07K2317/92C07K2317/94A61K2039/543C07K2317/41C07K2317/71C07K2317/72C07K2317/734C07K2317/75C07K2317/76C07K2317/90A61P11/00A61P11/06A61P29/00A61P31/04A61P35/00A61P37/00A61P37/06A61P37/08A61P7/06A61P9/10A61K39/39541C07K16/18
Inventor 阿列姆塞盖德·特鲁内弗兰西斯·约瑟夫·卡尔蒂莫西·戴维·琼斯詹姆斯·P·格雷格森
Owner NKT THERAPEUTICS
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