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Development of a chimeric cytokine receptor that captures IL-6 and enhances the antitumor response of CAR-T cells.
Yoshikawa, Toshiaki; Ito, Yusuke; Wu, Zhiwen; Kasuya, Hitomi; Nakashima, Takahiro; Okamoto, Sachiko; Amaishi, Yasunori; Zhang, Haosong; Li, Yang; Matsukawa, Tetsuya; Inoue, Satoshi; Kagoya, Yuki.
Afiliación
  • Yoshikawa T; Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan; Division of Immune Response, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
  • Ito Y; Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan; Division of Immune Response, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
  • Wu Z; Division of Immune Response, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
  • Kasuya H; Division of Immune Response, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
  • Nakashima T; Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan; Division of Immune Response, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan; Department of Hematology and Oncology, Nagoya City University Institute of Me
  • Okamoto S; Takara Bio Inc., Shiga 525-0058, Japan.
  • Amaishi Y; Takara Bio Inc., Shiga 525-0058, Japan.
  • Zhang H; Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan; Division of Immune Response, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan; Division of Cellular Oncology, Department of Cancer Diagnostics and Therapeut
  • Li Y; Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan; Division of Immune Response, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan; Division of Cellular Oncology, Department of Cancer Diagnostics and Therapeut
  • Matsukawa T; Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan; Division of Immune Response, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan; Department of Obstetrics and Gynecology, Nagoya University Graduate School of
  • Inoue S; Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan; Division of Immune Response, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan.
  • Kagoya Y; Division of Tumor Immunology, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo 160-8582, Japan; Division of Immune Response, Aichi Cancer Center Research Institute, Nagoya 464-8681, Japan; Division of Cellular Oncology, Department of Cancer Diagnostics and Therapeut
Cell Rep Med ; 5(5): 101526, 2024 May 21.
Article en En | MEDLINE | ID: mdl-38670095
ABSTRACT
The efficacy of chimeric antigen receptor (CAR)-engineered T cell therapy is suboptimal in most cancers, necessitating further improvement in their therapeutic actions. However, enhancing antitumor T cell response inevitably confers an increased risk of cytokine release syndrome associated with monocyte-derived interleukin-6 (IL-6). Thus, an approach to simultaneously enhance therapeutic efficacy and safety is warranted. Here, we develop a chimeric cytokine receptor composed of the extracellular domains of GP130 and IL6RA linked to the transmembrane and cytoplasmic domain of IL-7R mutant that constitutively activates the JAK-STAT pathway (G6/7R or G6/7R-M452L). CAR-T cells with G6/7R efficiently absorb and degrade monocyte-derived IL-6 in vitro. The G6/7R-expressing CAR-T cells show superior expansion and persistence in vivo, resulting in durable antitumor response in both liquid and solid tumor mouse models. Our strategy can be widely applicable to CAR-T cell therapy to enhance its efficacy and safety, irrespective of the target antigen.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T / Inmunoterapia Adoptiva / Interleucina-6 / Receptores Quiméricos de Antígenos Límite: Animals / Humans Idioma: En Revista: Cell Rep Med Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos T / Inmunoterapia Adoptiva / Interleucina-6 / Receptores Quiméricos de Antígenos Límite: Animals / Humans Idioma: En Revista: Cell Rep Med Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Estados Unidos