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Non-genetic engineering of cytotoxic T cells to target IL-4 receptor enhances tumor homing and therapeutic efficacy against melanoma.

Abstract

Adoptive transfer of cytotoxic T lymphocytes (CTLs) has been used as an immunotherapy in melanoma. However, the tumor homing and therapeutic efficacy of transferred CTLs against melanoma remain unsatisfactory. Interleukin-4 receptor (IL-4R) is commonly up-regulated in tumors including melanoma. Here, we studied whether IL-4R-targeted CTLs exhibit enhanced tumor homing and therapeutic efficacy against melanoma. CTLs isolated from mice bearing melanomas were non-genetically engineered with IL4RPep-1, an IL-4R-binding peptide, using a membrane anchor composed of dioleylphosphatidylethanolamine. Compared to control CTLs, IL-4R-targeted CTLs showed higher binding to melanoma cells and in vivo tumor homing. They also exerted a more rapid and robust effector response, including increased cytokine secretion and cytotoxicity against melanoma cells and enhanced reprogramming of M2-type macrophages to M1-type macrophages. Moreover, IL-4R-targeted CTLs efficiently inhibited melanoma growth and reversed the immunosuppressive tumor microenvironment. These results suggest that non-genetically engineered CTLs targeting IL-4R have potential as an adoptive T cell therapy against melanoma.

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  • Authors+Show Affiliations

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    Department of Biochemistry and Cell Biology, Department of Biomedical Science, CMRI, School Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, Republic of Korea.

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    Department of Nuclear Medicine, School Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, Republic of Korea.

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    Department of Biochemistry and Cell Biology, Department of Biomedical Science, CMRI, School Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, Republic of Korea.

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    Department of Biochemistry and Cell Biology, Department of Biomedical Science, CMRI, School Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, Republic of Korea.

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    Department of Biochemistry and Cell Biology, Department of Biomedical Science, CMRI, School Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, Republic of Korea.

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    Department of Nuclear Medicine, School Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, Republic of Korea.

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    Department of Physiology, School Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, Republic of Korea.

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    Department of Immunology, School of Medicine, Konkuk University, 268 Chungwon-daero, Chungju, Chungcheongbuk-do 27478, Republic of Korea.

    Department of Biochemistry and Cell Biology, Department of Biomedical Science, CMRI, School Medicine, Kyungpook National University, 680 Gukchaebosang-ro, Jung-gu, Daegu 41944, Republic of Korea. Electronic address: leebh@knu.ac.kr.

    Source

    Biomaterials 159: 2018 Mar pg 161-173

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    29329051