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CD38-targeted chimeric antigen receptor and application thereof

A chimeric antigen receptor and targeting technology, applied in the field of tumor cell immunotherapy, can solve the problems of poor persistence of CART cells, unsustainable treatment effect, and inability to effectively prevent anti-IgE reactions, so as to prevent anti-IgE reactions and prevent Effects of allergic reactions

Active Publication Date: 2021-10-26
BEIJING UNIV OF CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, due to the immunogenicity of the CAR transgene, the host's immune response to the murine single-chain variable region (ScFv) results in poor persistence of CAR T cells and the therapeutic effect is not long-lasting
In CAR-T cell therapy, humanized ScFv has been applied as a strategy to reduce CAR immunogenicity and subsequently improve efficacy, but it is not effective in preventing the occurrence of anti-IgE reactions leading to anaphylaxis

Method used

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  • CD38-targeted chimeric antigen receptor and application thereof
  • CD38-targeted chimeric antigen receptor and application thereof
  • CD38-targeted chimeric antigen receptor and application thereof

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Embodiment Construction

[0036] In order to enable those skilled in the art to better understand the technical solutions in the application, the present invention will be further described below in conjunction with the embodiments. Obviously, the described embodiments are only a part of the embodiments of the application, rather than all embodiments . Based on the embodiments in this application, all other embodiments obtained by persons of ordinary skill in the art without making creative efforts shall fall within the scope of protection of this application.

[0037] 1. Materials and methods

[0038] 1. Cell Lines and Cell Culture

[0039] The Phoenix-ECO cell line and PG13 cell line required for retroviral vector packaging were purchased from the American Tissue Culture Center (ATCC, Manassas, VA, USA). Both cell lines were cultured in DMEM (Gibco, USA) containing 10% fetal bovine serum (FBS, Gibco, USA) and used for retroviral vector packaging. Tumor cells RPMI-gfp-luc, Raji-luc, Daudi and K562-...

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Abstract

The invention relates to a CD38-targeted chimeric antigen receptor (CD38CAR) and application thereof. The amino acid sequence of a single-chain antibody containing a heavy chain variable region and a light chain variable region of the receptor is SEQ ID NO: 1 or SEQ ID NO: 2. A CAR-T cell prepared from the two CD38CARs disclosed by the invention has a specific killing effect on tumor cells, and the killing effect on the tumor cells is lasting.

Description

technical field [0001] The invention relates to the field of tumor cell immunotherapy, in particular to a chimeric antigen receptor targeting CD38 and its application. Background technique [0002] Multiple myeloma (MM) is a hematological malignancy characterized by the uncontrolled expansion of plasma cells in the bone marrow. Clinical manifestations of disease include signs of internal organ damage such as hypercalcemia, renal insufficiency, anemia, and / or osteolytic lesions. MM accounts for 1% of all cancers, with an incidence of 6-7 cases per 100,000 people, and is the second most common hematologic malignancy, with an estimated 34,920 new cases of the disease in the United States in 2021 Cases were confirmed and 15,600 MM-related deaths would have occurred. [0003] Over the past few decades, with the rapid development of new therapeutic approaches such as proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies (mABs), autologous stem cell t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K19/00C12N5/10A61K39/00A61P35/00
CPCC07K16/2896C07K14/7051C12N5/0636A61K39/001126A61P35/00C07K2317/622C07K2319/02C07K2319/03C07K2319/41C07K2319/33C07K2319/74C12N2510/00A61K2039/5156
Inventor 王建勋冯娅茹李晓瑞尚凤琴余卓营宋志茹童建松刘颖
Owner BEIJING UNIV OF CHINESE MEDICINE