Combinations of irs/stat3 dual modulators and anti pd-1/pd-l1 antibodies for treating cancer

A PD-L1, PD-1 technology, applied in the direction of antibodies, drug combinations, antibody medical components, etc., can solve problems such as unmet needs

Pending Publication Date: 2020-07-31
TYRNOVO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] There is an unmet need for combinations useful in the treatme...

Method used

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  • Combinations of irs/stat3 dual modulators and anti pd-1/pd-l1 antibodies for treating cancer
  • Combinations of irs/stat3 dual modulators and anti pd-1/pd-l1 antibodies for treating cancer
  • Combinations of irs/stat3 dual modulators and anti pd-1/pd-l1 antibodies for treating cancer

Examples

Experimental program
Comparison scheme
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preparation example Construction

[0184] During the preparation of the pharmaceutical compositions according to the invention, the active ingredient is usually mixed with a carrier or excipient, which may be solid, semi-solid or liquid material. Said compositions can be taken as tablets, pills, capsules, pellets, granules, powders, lozenges, sachets, cachets, elixirs, suspensions, dispersions, emulsions, solutions, syrups, aerosols (as solid or in a liquid medium), ointments containing, for example, up to 10% by weight of the active compound, soft and hard gelatin capsules, suppositories, sterile injectable solutions and sterile packaged powders. Each possibility represents a separate embodiment of the invention.

[0185] The carrier may be any conventionally used carrier and is limited only by chemical-physical considerations such as solubility and lack of reactivity with the compounds of the invention and route of administration. The choice of carrier will be dictated by the particular method used to admini...

Embodiment 1

[0208] Example 1: Compound 4 and pembrolizumab Combinatorial combination turns non-responsive tumors into responsive tumors and blocks tumor progression

[0209] Experimental system :

[0210] Patient-derived xenografts (PDX) of esophagogastric junction adenocarcinoma biopsies were implanted subcutaneously (SC) into NodScid mice. On the first day of treatment, peripheral blood mononuclear cells (PBMC) from the same patient were injected intravenously into the mice (double autologous).

[0211] ■ Fresh human primary esophagogastric junction adenocarcinoma biopsies were implanted subcutaneously (SC) into NSG mice (P0).

[0212] Subcutaneous Implantation of Human Primary Tumor Biopsy Samples in NodScid Mice

[0213] Tumors (P3) were extracted from mice, measured, cut into 1-2mm pieces and transferred to gentleMACS tubes containing sterile saline. Tumor volume adjusted to 1.5 mm with saline 3 Tumor volume / 100ul saline. The samples were dissociated with a gentleMACS Octo...

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Abstract

The present invention relates to the treatment of cancer using combination therapy comprising a dual modulator of Insulin Receptor Substrate (IRS) and signal transducer and activator of transcription3 (Stat3), in combination with an antibody against programmed cell death 1 (PD-1) protein, an anti-programmed cell death protein 1 ligand (PD-L1) antibody, or a combination thereof. The combination can be used to re-sensitize a tumor that may develop or has developed resistance to the anti-PD-1 and/or anti-PD-L1 antibody, by enhancing response of the tumor to the anti-PD-1 and/or anti-PD-L1 antibody, converting non- responding tumors to responders and/or blocking tumor progression.

Description

technical field [0001] The present invention relates to the treatment of cancer using a combination therapy comprising a dual modulator of insulin receptor substrate (IRS) and signal transducer and activator of transcription 3 (Stat3) in combination with a protein targeting programmed cell death 1 (PD-1 ) and / or a combination of antibodies against programmed cell death protein 1 ligand (PD-L1). The combination can be used to render tumors that may develop or have developed resistance to the anti-PD-1 antibody by enhancing the response of the tumor to the anti-PD-1 antibody, converting a non-responsive tumor into a responsive tumor, and / or blocking tumor progression. -1 and / or anti-PD-L1 antibody-resistant tumor resensitization. Background technique [0002] Tyrosine phosphorylation inhibitors are a class of protein tyrosine kinase inhibitors designed to mimic the tyrosine substrate, ATP, and can allosterically inhibit the enzyme (Levitzki et al., Science (1995), 267:1782 -...

Claims

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Application Information

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IPC IPC(8): A61K39/39A61K31/5415A61K31/165A61P35/00C07C327/44C07D279/08
CPCA61K39/3955A61K31/165A61K31/5415C07K16/2818C07D279/08A61K2039/505C07K2317/24A61P35/00A61K45/06A61K31/275A61K2300/00A61K31/137C07C327/44
Inventor 哈达斯·鲁文尼拉纳·库珀尔施米特伊扎克·哈威翁
Owner TYRNOVO LTD
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