Triple therapy to enhance cancer cell killing in low immunogenic cancers

A cell, cancer technology, applied in the fields of chemistry and medicine, which can solve the problems of high recurrence rate and poor effect

Pending Publication Date: 2022-01-04
DALIAN WANCHUN BULIN PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Glioblastoma is also relatively resistant to radiotherapy and chemotherapy, so there is a high rate of recurrence after treatment
In addition, the immune response of tumor cells is less effective in completely eradicating all tumor cells after resection and radiation therapy

Method used

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  • Triple therapy to enhance cancer cell killing in low immunogenic cancers
  • Triple therapy to enhance cancer cell killing in low immunogenic cancers
  • Triple therapy to enhance cancer cell killing in low immunogenic cancers

Examples

Experimental program
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Effect test

Embodiment 1

[0161] A single-arm clinical study using patients with glioblastoma. The rationale to be used is triple therapy: (1) inhibition of FPPS by zoledronic acid to produce antigen (phosphorylated antigen), (2) stimulation of dendritic cells by plinabulin to enhance antigen presentation, and (3) PD-1 / PD-L1 inhibitors to optimize the cytotoxic response of CD8 T cells.

[0162] A single-arm clinical study using patients with glioblastoma. The rationale to be used is triple therapy: (1) inhibition of FPPS by zoledronic acid to produce antigen (phosphorylated antigen), (2) stimulation of dendritic cells by plinabulin to enhance antigen presentation, and (3) PD-1 / PD-L1 inhibitors to optimize the cytotoxic response of γ-δ T cells.

[0163] Patients will be pretreated with one or more doses of zoledronic acid to induce the production of phosphorylated antigens. Patients will then be administered plinabulin to present phosphorylated antigen to (1) γ-δ T cells and (2) CD4 / DC8 T cells. Aft...

Embodiment 2

[0167] Plinabulin, an immune checkpoint inhibitor (PD-1 antibody), and FPPS were compared to plinabulin alone, PD-1 antibody alone, and a combination of plinabulin and PD-1 antibody. The synergistic effect of inhibitors (nitrobisphosphonates) was tested. The experiments were performed with 7- to 10-week-old mice that had been injected subcutaneously with glioblastoma multiforme cells. Six experimental groups were prepared, each containing 9 mice.

[0168] The 1st group administers normal saline; The 2nd group administers Plinabulin diluent (without Plinabulin); The 3rd group administration is dissolved in the diluent and the concentration is 7.5mg / kg Plinabulin; Group 4 was administered with PD-1 antibody; Group 5 was administered with Plinabulin / PD-1 antibody for combination therapy; Group 6 was administered with Plinabulin / PD-1 antibody / FPPS inhibitor for combination therapy treat. For the Plinabulin / PD-1 antibody / FPPS inhibitor combined treatment group (Group 6), mice we...

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Abstract

Disclosed herein are compositions and methods for treating diseases in need of enhanced immunogenicity. Some embodiments provided herein relate to compositions comprising a T cell activator and / or proliferative agent, one or more immune checkpoint inhibitors, and an FPPS inhibitor. Some embodiments relate to methods of treating cancer by co-administering plinabulin, one or more immune checkpoint inhibitors, and an FPPS inhibitor to a subject in need thereof.

Description

technical field [0001] The present invention relates to the fields of chemistry and medicine. More specifically, the present invention relates to compositions and methods for the treatment of diseases in which low immunogenicity is the limiting factor in inducing an adequate immune response. Background technique [0002] Interactions between malignant cells and the immune system include: elimination of cancer cells by the innate and adaptive immune system, especially by cytotoxic T lymphocytes (CTLs) that recognize specific tumor-associated antigens (TAAs); The balance between drugs and cancer cells; or the evasion of immune control, which allows cancer cells to escape, leading to the eventual clinical detection of cancer. Specific immunotherapies such as cytokine interleukin 2 can drive existing immune responses, while immune checkpoint inhibitors such as CTLA-4 (cytotoxic T lymphocyte-associated antigen 4) antibody, PD-1 (programmed cell death Protein 1) antibodies and P...

Claims

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Application Information

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Patent Type & AuthorityApplications(China)
IPC IPC(8): A61K31/496A61K39/00A61K39/395A61K35/00C07K16/28
CPCA61K31/496A61K2300/00A61K39/3955A61K31/675C07K16/2818A61K2039/505A61P35/00A61K2039/80A61K2039/545A61K39/39558C07K2317/76A61K45/06A61K31/663A61P25/00A61K31/497
Inventor雷蒙·穆汉拉勒黄岚
OwnerDALIAN WANCHUN BULIN PHARM CO LTD