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Novel chimeric receptor composition, recombinant vector, cell and application thereof

A chimeric receptor and chimeric antigen receptor technology, applied in the field of biomedicine, can solve problems such as inability to kill target cells, inability to effectively activate intracellular signals, etc., to solve tumor heterogeneity and reduce the possibility of factor storms. , the effect of increasing safety

Inactive Publication Date: 2021-11-09
SHANGHAI IMMUNOHEAD BIOTECHNOLOGY CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] NK cells express NKG2D on the surface, and activate downstream signals DAP10 and DAP12 by recognizing their ligands such as MICA or MICB to kill target cells. After the surface NKG2D recognizes its ligand, it cannot effectively activate the intracellular signal, so it cannot kill the target cell

Method used

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  • Novel chimeric receptor composition, recombinant vector, cell and application thereof
  • Novel chimeric receptor composition, recombinant vector, cell and application thereof
  • Novel chimeric receptor composition, recombinant vector, cell and application thereof

Examples

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preparation example Construction

[0054] An embodiment of the present invention provides a method for preparing the above-mentioned cells, including the step of transfecting the above-mentioned vectors into the cells.

[0055] An embodiment of the present invention provides the application of the above-mentioned chimeric receptor composition, nucleic acid sequence, vector or cell in the preparation of antitumor drugs.

Embodiment 1

[0059] This embodiment provides a novel chimeric receptor composition; the novel chimeric receptor composition (hereinafter referred to as Dual CAR, and its corresponding CAR-T cell is referred to as Dual CAR-T) includes an amino acid sequence of SEQ ID NO: Anti-CLDN18.2-CAR of ID NO.1 (traditional second-generation Claudin18.2 CAR molecule, hereinafter referred to as 21007), and the chimeric receptor sequence shown in SEQ ID NO.2-9 (structural sequence as shown in figure 1 shown), the specific amino acid sequence corresponds to the sequence name 21067-21074 in Table 1 below.

[0060] Table 1 Sequence information of anti-CLDN18.2-CAR and chimeric receptor composition

[0061]

[0062]

[0063]

[0064]

[0065] like figure 1 As shown, in addition to the chimeric antigen receptor with an amino acid sequence such as SEQ ID NO.1, the above chimeric receptor composition also includes the following sequence information:

[0066] (1) P2A, its amino acid sequence is as ...

Embodiment 2

[0087] This embodiment provides Dual CAR-T cells expressing the above-mentioned chimeric receptors, and its construction method includes the following steps:

[0088] 1. Construction of expression vector: The Dual CAR molecule and the backbone of the lentiviral vector were respectively constructed by CRO company using the whole gene synthesis technology. The Dual CAR fragment was cloned into a lentiviral vector by conventional molecular cloning methods, and the names of the constructed plasmids are shown in Table 1 above. The successful construction of each plasmid was verified by the full sequence verification of the insert fragment.

[0089] 2. Lentivirus Packaging and Titer Determination

[0090] first day:

[0091] 1) Inoculate 293T cells in a T75 culture flask with a quantity of 5×10 6 , the culture volume is 20ml;

[0092] the next day:

[0093] 2) Confirm that the confluence of 293T cells is about 70%-80% before virus packaging, and perform an equal volume change of ...

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PUM

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Abstract

The invention provides a novel chimeric receptor composition, a recombinant vector, a cell and application thereof. The novel chimeric receptor composition comprises a traditional chimeric antigen receptor and an NKG2D chimeric receptor comprising a full-length sequence of NKG2D, DAP10 and / or DAP12 or a truncated fragment, called Dual CAR for short. The chimeric receptor composition provided by the invention enables conventional CAR-T cells to express an NKG2D extracellular region and an intracellular signal region, enlarges a CAR-T antigen recognition spectrum, solves the problem of tumour heterogeneity, enhances the killing ability of CAR-T on tumour cells expressing target antigens, realizes lower-level factor release, reduces the possibility of factor storm, and increases the safety of CAR-T.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to a novel chimeric receptor composition, recombinant vector, cell and application thereof. Background technique [0002] Traditional tumor treatment methods include surgery, radiotherapy, chemotherapy, targeted therapy, etc.; in recent years, the development of immunotherapy has brought profound changes to the field of tumor treatment, especially the inhibition of CTLA-4 and PD-1 / PD-L1 pathways Immune checkpoint therapy represented by drugs and adoptive cell therapy represented by CAR-T. Adoptive cell therapy includes TIL, NK, TCR-T, Wait. Among them, CAR-T therapy targeting CD19 has achieved excellent clinical efficacy in B-cell tumors, and in 2017, two CAR-T products were approved by the FDA for the treatment of B-cell leukemia or lymphoma. [0003] Although CAR-T has made significant progress in hematological tumors, the incidence of side effects such as cytokine storms ...

Claims

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Application Information

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IPC IPC(8): C07K19/00C12N5/10A61K39/00A61P35/00
CPCC07K16/28C07K14/7051C07K14/7056C07K14/70503C12N5/0636A61K39/001102A61P35/00C07K2319/03C07K2319/33C07K2319/74C12N2510/00A61K2039/5156C07K14/70521C12N15/62C07K2319/50A61K39/4631A61K39/4611A61K39/4644
Inventor 李彦涛钟云鹏王有涛王玉晗易桥勇
Owner SHANGHAI IMMUNOHEAD BIOTECHNOLOGY CO LTD
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