Mitigation of cytokine release syndrome in immunotherapy

Recombinant nucleic acid molecules with hairpin loops and chimeric antigen receptors in CAR T cells address CRS and uncontrolled proliferation, improving cancer treatment safety and efficacy by regulating IL6 and GMCSF levels and controlling cell survival.

JP2025535441APending Publication Date: 2025-10-24MICROCRISPR PVT LTD
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Patent Information

Application Number
JP2025522924
Authority / Receiving Office
JP · JP
Patent Type
Applications
Current Assignee / Owner
Priority Date
2022-10-20
Filing Date
2023-10-20
Publication Date
2025-10-24

AI Technical Summary

Technical Problem

Conventional CAR T cell-based immunotherapies for cancer treatment face challenges such as severe systemic toxicity, including cytokine release syndrome (CRS) due to high levels of interleukin 6 (IL6) and granulocyte-monocyte colony-stimulating factor (GMCSF), leading to immune-related complications and neurotoxicity, and the risk of cancer relapse due to uncontrolled proliferation of engineered CAR T cells.

Method used

The use of recombinant nucleic acid molecules with hairpin loop structures and chimeric antigen receptors to regulate IL6 and GMCSF levels, incorporating short hairpin RNA sequences to inhibit cytokine production and signaling, and a safety switch mechanism to control CAR T cell proliferation.

Benefits of technology

Reduces cytokine storm during immunotherapy, minimizing toxicity and prolonging the effectiveness of CAR T cells, thereby enhancing cancer treatment safety and efficacy by reducing the risk of relapse.

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Abstract

The present invention discloses a recombinant nucleic acid molecule encoded by at least ORFs (100, 100a) for reducing cytokine storm during immunotherapy. The recombinant nucleic acid molecule comprises at least one first hairpin loop structure, at least one second hairpin loop structure, and a first promoter (120). The first hairpin loop structure is formed by one or more first short hairpin RNA (130a) sequences. The first hairpin loop structure regulates the amount of interleukin 6 (IL6) cytokine during immunotherapy. The second hairpin loop structure is formed by one or more second short hairpin RNA (130b) sequences. The second hairpin loop structure regulates the amount of granulocyte-monocyte colony-stimulating factor (GMCSF) cytokine during immunotherapy and is located either upstream or downstream of the first hairpin loop structure. The first promoter (120) is located upstream of the first and second hairpin loop structures.
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