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Application of pharmaceutical composition in preparation of therapeutic drug for tumor insensitive to PD-1 antibody immunotherapy

A technology of PD-1 and immunotherapy, applied in the field of medicine, can solve the problem of insensitivity of antibody immunotherapy and achieve the effect of inhibiting tumor growth

Pending Publication Date: 2020-09-29
SUN YAT SEN UNIV CANCER CENT
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The present invention aims to solve the problem that some tumor patients are not sensitive to PD-1 antibody immunotherapy, and provides a targeted treatment plan for tumors with primary drug resistance to PD-1 antibody therapy

Method used

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  • Application of pharmaceutical composition in preparation of therapeutic drug for tumor insensitive to PD-1 antibody immunotherapy
  • Application of pharmaceutical composition in preparation of therapeutic drug for tumor insensitive to PD-1 antibody immunotherapy

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1 The influence of key driver genes Fgf3, Fgf4, and Fgf15 in the chromosome 11q13.3 segment on PD-1 antibody treatment

[0027] 1. Experimental materials:

[0028] (1) Tumor cell line: In this experiment, the classic mouse tumor cell line MC38 used in the basic research of immunotherapy was used.

[0029] (2) Experimental mice: C57BL / 6J mice.

[0030] (3) Drug: murine PD-1 antibody, clone number G4C2.

[0031] (4) Lentiviral transfection system: murine Fgf3, Fgf4, Fgf15 overexpression lentivirus and control empty vector virus.

[0032] 2. Experimental group:

[0033] Tumor cells overexpressing the empty vector and tumor cells overexpressing mouse Fgf3, Fgf4, and Fgf15 were subcutaneously formed in C57BL / 6J mice, and they were divided into two groups:

[0034] (1) Control group: given IgG control treatment;

[0035] (2) Treatment group: treated with murine PD-1 antibody.

[0036] 3. Experimental steps:

[0037] (1) Construction of cell lines stably overexp...

Embodiment 2

[0043] Example 2 PD-1 antibody and LY2874455 have a combined therapeutic effect on tumors with overexpressed Fgf15

[0044] 1. Experimental materials:

[0045] (1) Tumor cell line: Same as Example 1.

[0046] (2) Experimental mice: same as in Example 1.

[0047] (3) Drug: murine PD-1 antibody, clone number G4C2; LY2874455.

[0048] (4) Lentiviral transfection system: murine Fgf15 overexpression lentivirus and control empty vector virus.

[0049] 2. Experimental group:

[0050] Tumor cells overexpressing the empty vector and tumor cells overexpressing mouse Fgf15 were subcutaneously formed into tumors in C57BL / 6J mice, and each was divided into 4 groups:

[0051] (1) Control group: given IgG control treatment;

[0052] (2) Treatment group 1: treated with murine PD-1 antibody;

[0053] (2) Treatment group 2: LY2874455 treatment;

[0054] (2) Treatment group 3: treated with mouse PD-1 antibody combined with LY2874455;

[0055] 3. Experimental steps:

[0056] (1) Construc...

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PUM

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Abstract

The invention discloses application of a pharmaceutical composition in preparation of a therapeutic drug for a tumor insensitive to PD-1 antibody immunotherapy, and particularly relates to applicationof a PD-1 antibody combined LY2874455 in preparation of a drug for treating a chromosome 11q13.3 segment amplified tumor. Advanced solid tumors include esophageal squamous carcinoma, colorectal cancer, melanoma, head and neck squamous carcinoma or bladder cancer and the like. The anti-PD-1 antibody and LY2874455 combined medication scheme can be used for the tumor which is amplified in the chromosome 11q13.3 segment and is insensitive to PD-1 antibody immunotherapy, and compared with single-drug treatment, tumor growth is remarkably inhibited, so that a patient ineffective to the PD-1 antibody can benefit from the combined therapy.

Description

technical field [0001] The invention belongs to the technical field of medicine. More specifically, it relates to the application of PD-1 antibody combined with LY2874455 in the preparation of drugs for the treatment of tumors insensitive to PD-1 antibody immunotherapy, and the tumor insensitive to PD-1 antibody immunotherapy specifically refers to chromosome 11q13.3 Tumors with segmental amplification. Background technique [0002] Immunotherapy is an emerging tumor treatment method, and PD-1 (programmed cell death protein 1) is a common target of immunotherapy. PD-1 is an immunosuppressive receptor mainly expressed on the surface of T cells, B cells, monocytes and NK cells. When activated, PD-1 can activate tumor antigen-specific T cells and promote tumor immune escape. PD-1 antibody can release the immunosuppressive effect of this pathway by competitively binding to PD-1, and restore the anti-tumor immunity of T cells. PD-1 antibody is an immune checkpoint inhibitor, w...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61P35/00A61K31/4439
CPCA61K39/39558A61K31/4439A61P35/00A61K2300/00
Inventor 徐瑞华王峰赵齐王英男
Owner SUN YAT SEN UNIV CANCER CENT
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