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Chimeric antigen receptor with MAGE-A4 specificity and application thereof

A MAGE-A4, chimeric antigen receptor technology, applied in medical preparations containing active ingredients, antibody medical ingredients, DNA/RNA fragments, etc., can solve problems such as unsatisfactory

Pending Publication Date: 2022-03-11
REGENERON PHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] Unmet need for new targeting agents based on CARs that specifically bind to the MAGE-A4 antigen and methods for the production and use of such agents in therapeutic and diagnostic settings

Method used

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  • Chimeric antigen receptor with MAGE-A4 specificity and application thereof
  • Chimeric antigen receptor with MAGE-A4 specificity and application thereof
  • Chimeric antigen receptor with MAGE-A4 specificity and application thereof

Examples

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preparation example Construction

[0144] Preparation of antigen-binding domains

[0145] The antigen binding domains of chimeric antigen receptors of the present disclosure are specific for a particular antigen (eg, MAGE-A4) and can be prepared by any antibody production technique known in the art. In certain embodiments, one or more of the individual components (eg, heavy and light chains) of the corresponding antibodies of the disclosure are derived from chimeric, humanized, or fully human antibodies. Methods for making such antibodies are well known in the art. For example, VELOCIMMUNE can be used TM Techniques One or more of the heavy and / or light chains are produced. Use VELOCIMMUNE TM technology (or any other technique for antibody production by others), high affinity chimeric antibodies are initially isolated to a specific antigen (eg, MAGE-A4) with human variable regions and mouse constant regions. Antibodies are characterized and selected for desired properties including affinity, selectivity, epi...

example

[0202] The following examples are presented to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the methods and compositions of the disclosure, and are not intended to limit the scope of what the inventors regard as their invention. Efforts have been made to ensure accuracy with respect to numbers used (eg, amounts, temperature, etc.), but some experimental errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, molecular weight is average molecular weight, temperature is in degrees Celsius, and pressure is at or near atmospheric.

example 1

[0203] Example 1: Generation of anti-MAGE-A4 antibodies

[0204] Genetically modified mice (e.g., including human immunoglobulins encoding Anti-MAGE-A4 antibodies were obtained by engineered mice with DNA of variable region of protein heavy chain and κ light chain.

[0205] After immunization, splenocytes were harvested from each mouse and either (1) fused with mouse myeloma cells to maintain their viability and form hybridomas and screened for MAGE-A4 specificity or (2) using human MAGE-A4 fragments B cells are sorted as a sorting reagent that binds and identifies reactive antibodies (antigen positive B cells) (as described in US Patent Publication No. 2007 / 0280945A1).

[0206] Chimeric antibodies against MAGE-A4 were initially isolated with human variable regions and mouse constant regions. Antibodies are characterized and selected for desired characteristics including affinity, selectivity, etc. If desired, fully human anti-MAGE-A4 antibodies are produced by replacing th...

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Abstract

The MAGE-A4 or the melanoma associated antigen A4 is a cancer-testicular antigen (CTA) on the X chromosome. The present disclosure provides MAGE-A4 specific chimeric antigen receptors and cells expressing such chimeric antigen receptors. In certain embodiments, engineered cells expressing the chimeric antigen receptors of the present disclosure are capable of inhibiting the growth of MAGE-A4 expressing tumors. The engineered cells of the present disclosure are useful in the treatment of diseases and conditions in which an upregulated or induced MAGE-A4 targeting immune response is desirable and / or therapeutically beneficial. For example, engineered cells expressing the MAGE-A4 specific chimeric antigen receptors of the present disclosure can be used to treat various cancers.

Description

[0001] Cross References to Related Applications [0002] This application claims U.S. Provisional Patent Application No. 62 / 878,125, filed July 24, 2019; U.S. Provisional Patent Application No. 63 / 020,177, filed May 5, 2020; and 63 / 021,407, each of which is hereby incorporated by reference in its entirety for all purposes. [0003] References to Sequence Listings [0004] This application incorporates by reference the file 10600WO01-Sequence.txt created on July 24, 2020 and containing 123,650 byte sequences as a list submission in computer readable form. technical field [0005] The present disclosure provides chimeric antigen receptors (CARs) and engineered cells comprising such CARs, which are specific for melanoma-associated antigen A4 (MAGE-A4), and methods of use thereof. Background technique [0006] MAGE-A4 or melanoma-associated antigen A4 is the cancer-testis antigen (CTA) on the X chromosome. The function of MAGE-A4 is unknown, but it may be involved in cell ...

Claims

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Application Information

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IPC IPC(8): C07K19/00C12N15/62C12N15/13C12N15/867C12N5/10A61K39/00A61K39/395A61K45/06A61P35/00
CPCC07K16/30C07K14/7051C12N15/86C12N5/0638A61K39/39558A61K45/06A61P35/00C07K2319/02C07K2319/03C07K2319/33C07K2317/622C07K2317/56C07K2317/565C12N2510/00C12N2740/15043A61K2039/505A61K2039/876A61K2039/804A61K2039/57A61K39/464486A61K39/4611A61K2239/31A61K39/4631A61K2239/46C12N5/0636A61K2239/57A61K2239/38A61K2239/13A61K2300/00C07K16/2833C07K2317/34C07K2317/73C07K2317/55C07K14/70517C07K14/70578C07K14/70521C07K2317/24
Inventor K·布雷F·德尔菲诺D·迪利洛T·C·米格尔
Owner REGENERON PHARM INC
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