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

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...

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Bibliographic Details
Published in:Biomaterials 2018-03, Vol.159, p.161-173
Main Authors: Gunassekaran, Gowri Rangaswamy, Hong, Chae-Moon, Vadevoo, Sri Murugan Poongkavithai, Chi, Lianhua, Guruprasath, Padmanaban, Ahn, Byung-Cheol, Kim, Ha-Jeong, Kang, Tae Heung, Lee, Byungheon
Format: Article
Language:English
Subjects:
Adoptive T cell therapy
Apoptosis - physiology
Cell Line, Tumor
Cell Proliferation - physiology
Cytokines - metabolism
Cytotoxic T lymphocytes
Humans
Immunotherapy - methods
Interferon-gamma - metabolism
Interleukin-4 receptor
Melanoma
Melanoma - metabolism
Receptors, Interleukin-4 - metabolism
T-Lymphocytes, Cytotoxic - metabolism
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Summary: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. [Display omitted]
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2018.01.013