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Fusion protein comprising Anti-mesothelin antibody, Anti-cd3 antibody or Anti-egfr antibody, bispecific or trispecific antibody comprising same, and uses thereof

A fusion protein and specific technology, applied in the field of fusion proteins, can solve the problems of high killing effect and mismatch of tumor cells, and achieve the effect of excellent tumor killing and growth inhibition effect.

Pending Publication Date: 2021-12-31
GREEN CROSS CORP THE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] As a result of intensive research to solve the problems of existing bispecific antibodies, the inventors developed a fusion protein in which the heavy and light chains of the antibody are connected by a linker and thus contained as a single chain, and the fusion protein comprising the protein bispecific or trispecific antibodies; and found that these fusion proteins and antibodies solve the problem of mismatch, and have a high killing effect on tumor cells, thereby completing the present invention

Method used

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  • Fusion protein comprising Anti-mesothelin antibody, Anti-cd3 antibody or Anti-egfr antibody, bispecific or trispecific antibody comprising same, and uses thereof
  • Fusion protein comprising Anti-mesothelin antibody, Anti-cd3 antibody or Anti-egfr antibody, bispecific or trispecific antibody comprising same, and uses thereof
  • Fusion protein comprising Anti-mesothelin antibody, Anti-cd3 antibody or Anti-egfr antibody, bispecific or trispecific antibody comprising same, and uses thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0155] Example 1. Production of anti-MSLN / anti-CD3 bispecific antibodies and anti-EGFR / anti-MSLN / anti-CD3 trispecific antibodies

Embodiment 11

[0156] Example 1.1. Production of MSLN, CD3 or EGFR-specific antibodies

[0157] To select MSLN-specific antibodies, mice were immunized with recombinant human MSLN, from which B cells were subsequently extracted to clone various antibody genes. Using phage display, these genes were used to prepare antibody libraries, and cloning of antibodies binding to recombinant human MSLN was performed. Finally, antibody humanization was performed to obtain the HMI323 clone consisting of the amino acid sequence of SEQ ID NO:1 encoded by the gene consisting of the nucleotide sequence of SEQ ID NO:4.

[0158] To select antibodies specific for human and monkey CD3, the mouse SP34 antibody was humanized and selected for antibodies that bind CD3 with various affinities. Among them, clone A07 consisting of the amino acid sequence of SEQ ID NO: 21, clone A15 consisting of the amino acid sequence of SEQ ID NO: 11, and clone E15 consisting of the amino acid sequence of SEQ ID NO: 23 were obtained...

Embodiment 12

[0160] Example 1.2. Transfection of vectors for antibody expression

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Abstract

The present invention relates to: a fusion protein comprising a fragment of an anti-mesothelin antibody, an anti-CD3 antibody or an anti-EGFR antibody; a bispecific antibody that is specific to mesothelin and CD3; a trispecific antibody that is specific to mesothelin, CD3 and EGFR; and uses thereof. The bispecific or trispecific antibody according to the present invention can be prepared in a high yield and with high purity, and has excellent tumor killing and growth inhibitory effects, and thus can be effectively used in cancer treatment.

Description

technical field [0001] The present invention relates to fusion proteins comprising anti-mesothelin antibody, anti-CD3 antibody or anti-EGFR antibody; Trispecific antibodies; and uses thereof. Background technique [0002] In anticancer therapy, monoclonal antibodies, as the first cancer immunotherapy, have shown excellent effects not only in solid cancers but also in blood cancers; however, they still have limitations. In this regard, technologies are introduced in which the Fc region of an antibody is engineered to enhance the antibody-dependent cytotoxicity (ADCC) effect of the antibody, or in which bispecific or trispecific antibodies are developed This allows a single antibody to approach multiple targets. [0003] Bispecific antibodies are antibodies that can bind to two different antibodies simultaneously and can be engineered so that immune cells (such as T cells) are only toxic to specific target cells (such as cancer cells) and not to other normal cells. Such bis...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K16/28C07K16/30A61P35/00A61K39/00
CPCA61P35/00C07K16/30C07K2317/35C07K2317/31C07K2317/60C07K16/2863C07K16/2809C07K2317/526C07K2317/24C07K2317/33C07K2317/92C07K2317/73A61K2039/505C07K2317/94C07K2317/522C07K2317/565C07K16/18C07K2319/30
Inventor 林良美李世奈元锺和朴用礼尹爱吝李秀娥林玉宰林昭贞金妏经
Owner GREEN CROSS CORP THE
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