Combination immune therapy and cytokine control therapy for cancer treatment

A cancer, cell-based technology, applied in the direction of blood/immune system cells, genetically modified cells, receptors/cell surface antigens/cell surface determinants, etc., can solve problems such as impossibility, poorly localized, ineffective or suboptimal

Pending Publication Date: 2020-06-05
ENLIVEX THERAPEUTICS LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

These lesions may be difficult or impossible to treat by ablative methods due to inaccessibility, infiltration, and / or poor localization
Chemo / radiotherapy currently selected for the treatment of certain metastatic malignancies is often ineffective or suboptimal and has significant disadvantages associated with particularly deleterious and / or potentially fatal side effects

Method used

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0719] Example 1: Generation of apoptotic cells

[0720] Purpose: to generate early apoptotic cells

[0721] Method: The method for preparing an early apoptotic cell population is documented in detail in International Publication WO 2014 / 087408 and U.S. Application Publication US2015 / 0275175-A1, see, for example, the Methods section "Preparation of an Early Apoptotic Cell Population" and "Apoptosis Generation of Cells" (paragraphs [0223] to [0288] and Examples 11, 12, 13 and 14, which are incorporated herein in their entirety).

[0722] The flow chart shown in Figure 1 provides an overview of one embodiment of the steps used in the process of generating an early apoptotic cell population, wherein an anticoagulant is included in the thawing and induction of apoptosis steps. As described in detail in Example 14 of International Publication No. WO2014 / 087408 and U.S. Application Publication No. US US-2015-0275175-A1, early apoptotic cell populations were prepared, either when fr...

Embodiment 2

[0770] Example 2: Effect of apoptotic cells on cytokine release in an in vitro cytokine storm model

[0771] Objective: To test the response of apoptotic cells to cytokine storm markers (cytokines IL-6, IL-10, MIP-1α, IL-8, TNF, -α, MIP-1β, MCP-1 and IL-9) levels.

[0772] method:

[0773] Cell Lines and Culture Reagents

[0774] Human lymphoma cell line Raji (eCACC, UK, accession number 85011429), human cervical adenocarcinoma cell line HeLa (ATCC, USA, number: CCL-2) and HeLa-CD19 (ProMab, USA, catalog number PM-Hela-CD19 ) in supplemented with 10% FBS (Gibco, ThermoFisher Scientific, South America, catalog number 12657-029), 2mM GlutaMAX (Gibco, ThermoFisher Scientific, USA, catalog number 35050-038) and 100U / ml penicillin+100U / ml streptomycin RPMI 1640 (Gibco, ThermoFisher Scientific, USA, catalog number 31870-025) (hereinafter referred to as "complete medium") (Gibco, ThermoFisher Scientific, USA, catalog number 15140-122). During the standard culture process, 1 μg / ml...

Embodiment 3

[0784] Example 3: Effect of Apoptotic Cells on Cytokine Storm without Negative Effect on CAR-T Cell Efficacy

[0785] Purpose: To test the effect of apoptotic cells or supernatants derived from apoptotic cells on cytokine storm marker cytokines and CAR T cell efficacy against tumor cells

[0786] method:

[0787] T4+CAR T-cells

[0788] A solid tumor model reported to induce a cytokine storm in mice was used (van der Stegen et al., 2013, supra). In this model, T cells are engineered with chimeric antigen receptors (CARs) targeting some ErbB dimers (T4 + CAR-T cells), these dimers 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 the chimeric T4+ receptor is constructed and transduced into isolated T cells to generate T4+ CAR T cells. For the experiments performed here, T4+ CAR T cells were purchased from CreativeBiola...

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Abstract

Compositions disclosed herein, and methods of use thereof included those for inhibiting or reducing the incidence of cytokine release syndrome or cytokine storm in a subject undergoing CAR T-cell therapy, methods of treating a cancer or tumor, methods of reducing tumor load, methods of reducing the size or growth rate of a cancer or a tumor, and methods of extending of the survival of a subject suffering from a cancer or tumor, wherein the subjects are administered compositions comprising apoptotic cells or apoptotic cell supernatants. Compositions and methods of use thereof may increase the efficacy of a CAR T-cell cancer therapy. Disclosed herein are also compositions and methods of use thereof for decreasing or inhibiting cytokine production in a subject experiencing cytokine release syndrome or cytokine storm. In certain instances, compositions may include additional chemotherapeutic or immunomodulatory agents.

Description

[0001] Related areas [0002] Disclosed herein are compositions and methods thereof for inhibiting or reducing the incidence of cytokine release syndrome (CRS) or cytokine storm in a subject undergoing CAR T cell cancer therapy. Additionally, disclosed herein are compositions and methods for reducing or inhibiting cytokine production in a subject experiencing cytokine release syndrome or cytokine storm. In addition, the compositions disclosed herein are useful for treating, preventing, inhibiting the growth of, or reducing the incidence of cancer or tumors in a subject. The compositions are useful for increasing the survival of subjects with cancer or tumors. The compositions used can be administered alone or in combination with other chemotherapies. The methods disclosed herein include those comprising administering a composition comprising apoptotic cells or apoptotic cell supernatant alone or comprising administering a composition comprising apoptotic cells or apoptotic cel...

Claims

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Application Information

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IPC IPC(8): A61K35/15A61K35/17A61P37/06
CPCA61K39/39558A61K45/06A61K2039/505A61P37/06C07K16/2887C12N5/0636C12N2501/91C12N2529/00C12N2510/00C07K14/7051C07K2317/622A61P35/04A61K2239/48A61K39/46434A61K39/4621A61K39/464412C12N5/0645A61K2239/59A61K39/464406A61K2239/31A61K2239/38A61K39/464419A61K39/4631A61K39/4614A61K39/4622A61K39/4611A61K2300/00C12N2501/04A61K39/39541C12N2523/00A61P35/00A61K35/17A61K39/0011A61K2039/5158
Inventor S·诺维克D·梅沃拉克
Owner ENLIVEX THERAPEUTICS LTD
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