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Combination cancer therapy and cytokine control therapy for cancer treatment

A cancer treatment, cancer technology, applied in animal cells, vertebrate cells, blood/immune system cells, etc.

Pending Publication Date: 2022-07-08
伊利威克斯疗法罗德有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] There remains an unmet need for compositions and methods for treating, preventing, inhibiting the growth of, or reducing the incidence of cancer or tumors in a subject

Method used

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  • Combination cancer therapy and cytokine control therapy for cancer treatment
  • Combination cancer therapy and cytokine control therapy for cancer treatment
  • Combination cancer therapy and cytokine control therapy for cancer treatment

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0730] Example 1: Apoptotic Cell Generation

[0731] Objective: To generate early apoptotic cells.

[0732] Methods: Methods for preparing early apoptotic cell populations have been well documented in International Publication No. WO 2014 / 087408 and US Application Publication No. US2015 / 0275175-A1, see eg "Preparation of Early Apoptotic Cell Populations" and "Apoptotic Cell Populations" before the Examples. Generation of apoptotic cells" (paragraphs [0223]-[0288]) and Examples 11, 12, 13, and 14, the disclosures of which are incorporated herein in their entirety.

[0733]The flow chart presented in Figure 1 provides an overview of one example of the steps used during the process of generating an early apoptotic cell population, wherein an anticoagulant is included in the thawing and apoptosis induction steps. As described in detail in Example 14 of International Publication No. WO2014 / 087408 and US Application Publication No. US US-2015-0275175-A1, early apoptotic cell popula...

example 2

[0783] Example 2: Effects of Apoptotic Cells on Cytokine Storm in an In Vitro Cytokine Storm Model

[0784] Objective: To investigate the effect of apoptotic cells on cytokine storm markers (cytokines IL-6, IL-10, MIP-1α, IL-8) in cytokine storm induced in the LPS sterile model of macrophage activation syndrome. , TNF-α, MIP-1β, MCP-1 and IL-9) levels were tested.

[0785] method

[0786] Cell Lines and Culture Reagents

[0787] The human lymphoma cell line Raji (eCACC, UK, accession number 85011429), human cervical adenocarcinoma cell line HeLa (ATCC, USA, number: CCL-2) and HeLa-CD19 (Prime Biotech Co., Ltd., USA) , Cat. No. PM-Hella-CD19) hereinafter referred to as "complete medium" supplemented with 10% FBS (Gibco, ThermoFisher Scientific, South America, Cat. No. 12657-029), 2 mM GlutaMAX (Gibco, Thermo Fisher Scientific, USA, catalog number 35050-038) and 100 U / ml penicillin + 100 U / ml streptomycin (Gibco, Thermo Fisher Scientific, USA, catalog number 15140-122 ) in R...

example 3

[0797] Example 3: Effect of Apoptotic Cells on Cytokine Storm Without Negative Effects on CAR-T Cell Efficacy

[0798] Objective: To test the effect of apoptotic cells or supernatant derived from apoptotic cells on cytokine storm marker cytokines and the efficacy of CAR T cells against tumor cells.

[0799] method:

[0800] T4+CAR T cells

[0801] A solid tumor model reported to induce cytokine storm in mice was used (van der Stegen et al., 2013 supra). In this model, T cells are engineered with a chimeric antigen receptor (CAR) targeting certain ErbB dimers (T4 + CAR-T cells), which are often highly upregulated in certain solid tumors such as head and neck tumors and ovarian cancer. T cells were isolated from PBMC isolated from peripheral blood using CD3 microbeads. A vector containing a chimeric T4+ receptor was constructed and transduced into isolated T cells, resulting in T4+ CAR T cells. For the experiments performed in this paper, T4+ CAR T cells were purchased from...

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PUM

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Abstract

The compositions disclosed herein and methods of use thereof include those that inhibit or reduce the incidence of cytokine release syndrome (CRS) or cytokine storm in a subject undergoing CAR T cell therapy, methods of treating cancer or tumors, methods of reducing tumor load, methods of treating cancer or tumors, and methods of treating cancer or tumors. Methods of reducing the size or growth rate of a cancer or tumor, and methods of extending the survival of a subject suffering from a cancer or tumor, where the subject is administered a composition comprising apoptotic cells or apoptotic cell supernatant. The compositions and methods of use thereof can increase the efficacy of CAR T cell cancer therapies. Also disclosed herein are methods of slowing, reducing, inhibiting, or eliminating metastatic spread of a cancer or tumor in a subject comprising administering a combination therapy comprising a population of early apoptotic cells and one or more cancer therapeutic agents.

Description

technical field [0001] Disclosed herein is a method for inhibiting cytokine release syndrome (CRS) or cytokine storm or reducing all symptoms in a subject undergoing cancer therapy, such as, but not limited to, chimeric antigen receptor expressing T cell (CAR T cell) cancer therapy. Compositions and methods for the incidence of CRS or cytokine storm. Further, disclosed herein are compositions and methods for reducing or inhibiting cytokine production in subjects experiencing cytokine release syndrome or cytokine storm. Further, the compositions disclosed herein can be used to treat, prevent, inhibit the growth of, or reduce the incidence of a cancer or tumor in a subject. The compositions can be used to increase survival in subjects with cancer or tumors. The compositions used can be administered alone or in combination with other cancer therapeutics or chemotherapy. The methods disclosed herein include those comprising administering a combination therapy comprising an earl...

Claims

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Application Information

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IPC IPC(8): C12N5/078
Inventor S·诺维克D·梅沃拉赫
Owner 伊利威克斯疗法罗德有限公司