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Combination immune therapy and cytokine control therapy for cancer treatment

A technology of cytokines and cells, which is applied in the field of compositions that reduce or inhibit the production of cytokines, and can solve the problems of affecting the activity and proliferation of CART-cells, the inability to effectively control cytokine release syndrome, and the limited ability to inject anti-inflammatory drugs, etc.

Pending Publication Date: 2018-01-02
ENLIVEX THERAPEUTICS LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, steroids may affect CAR T-cell activity and / or proliferation and put patients at risk for sepsis and opportunistic infections
Anti-inflammatory drugs may not be effective in controlling cytokine release syndrome, or cytokine storm, because cytokine storms include very large numbers of cytokines, but the ability to infuse patients with anti-inflammatory drugs is limited

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

[0471] Example 1: Apoptotic cell therapy prevents cytokine storm in subjects administered CAR T-cell therapy

[0472] Materials and methods

[0473] recombinant DNA construct

[0474] Develop CARs that retarget T-cells specific to specific tumor-associated antigens. Control CARs were developed that directed T-cells to unrelated tumor-associated antigens. CARs used for background were armed CAR T or 4th passage CAR T-cells. In one embodiment, cells are also engineered to express the extracellular structure of the IL-4 receptor alpha subunit linked to the transmembrane and intracellular domains of the beta-chain used by the IL-2 and IL-15 receptors domain, allowing the expansion of T-cells by adding IL-4.

[0475] Retroviral transduction and culture of T4+ T-cells

[0476] Blood samples were obtained from healthy volunteers and cancer patients. T-cells can be activated prior to gene transfer using CD3 / CD28 coated paramagnetic beads (1:1 bead / cell ratio; Life Technologies) or...

Embodiment 2

[0496] Example 2: Effect of apoptotic cells on cytokine storm without negative impact on CAR-T cell potency

[0497] Objective: To test the effect of apoptotic cells or supernatants derived from apoptotic cells on cytokine storm marker cytokines and CAR T-cell potency against tumor and cancer cells.

[0498] method:

[0499] A solid tumor model reported to induce a cytokine storm in mice was utilized (van der Stegen et al., 2013ibid). In this model, T cells are engineered with chimeric antigen receptors (CARs) 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. Vectors containing chimeric T4+ receptors were constructed and transduced into isolated T-cells, resulting in T4+ CAR T-cells. For the experiments performed here, T4+ CAR T-cells were purchased (Creative Biolabs (NY USA) or Prom...

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PUM

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Abstract

Compositions disclosed herein, and methods of use thereof include those for inhibiting or reducing the incidence of cytokine release syndrome or cytokine storm in a subject undergoing CAR T-cell therapy, wherein the subjects are administered compositions including apoptotic cells or apoptotic cell supernatants. In certain instances compositions and methods of use thereof disclosed herein do not reduce the efficacy of the 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 including administration of a composition including apoptotic cells or an apoptotic cell supernatant.

Description

[0001] areas of concern [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 receiving CAR T-cell cancer therapy. Further, disclosed herein are compositions and methods for reducing or inhibiting cytokine production in a subject experiencing cytokine release syndrome or cytokine storm. The methods disclosed herein include those comprising administering a composition comprising apoptotic cells or supernatants of apoptotic cells in combination with CART-cell therapy. Background of the invention [0003] While the standard treatments for cancer are surgery, chemotherapy and radiation therapy, improved approaches such as targeted immunotherapy are currently being developed and tested. One promising technique uses adoptive cell transfer (ACT), in which immune cells are modified to recognize and attack their tumors. One example of ACT is the engineering of a patient...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K35/17A61P37/06
CPCA01K67/0271A61K35/00C12N2502/1114C12N2502/30C12N2510/00A01K2227/105A01K2267/0331C12N5/0638A61P37/06Y02A50/30A61K39/4611A61K2239/31A61K39/4631A61K2239/59A61K2239/38A61K39/464406G01N33/6863A61K2035/122A61K2035/124A61K35/17A61P31/00A61P19/02A61P29/00A61P17/00
Inventor S·诺维克D·梅沃拉克
Owner ENLIVEX THERAPEUTICS LTD
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