Combination of Expanded Allogeneic NK Cells and T Cell-Based Immunotherapy Exert Enhanced Antitumor Effects
Immunotherapies based on immune checkpoint blockade, neoantigen-reactive tumor-infiltrating lymphocytes and T cell receptor-engineered T cells (TCR-T) have achieved favorable clinical outcomes in tumor treatment. However, sustained immune response and tumor regression have been observed only in a fe...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/1/251 |
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| author | Xiao Wang Xuejiao Yang Yueping Wang Yunshuo Chen Ying Yang Siqi Shang Wenbo Wang Yueying Wang |
| author_facet | Xiao Wang Xuejiao Yang Yueping Wang Yunshuo Chen Ying Yang Siqi Shang Wenbo Wang Yueying Wang |
| author_sort | Xiao Wang |
| collection | DOAJ |
| description | Immunotherapies based on immune checkpoint blockade, neoantigen-reactive tumor-infiltrating lymphocytes and T cell receptor-engineered T cells (TCR-T) have achieved favorable clinical outcomes in tumor treatment. However, sustained immune response and tumor regression have been observed only in a few patients due to immune escape. Natural killer (NK) cells can mediate direct tumor lysis and target cancer cells with low or no expression of human leukocyte antigen class I (HLA-I) that are no longer recognized by T cells during immune escape. Therefore, the combination of T cell-based immunotherapy and NK cell therapy is a promising strategy for improving antitumor response and response rate. However, allogeneic NK cells for adoptive cell therapy have been limited by both the required cell number and quality. Here, we developed an efficient manufacturing system that relies on genetically modified K562 cells for the expansion of high-quality NK cells derived from peripheral blood mononuclear cells. NK cells with the optimal expansion and activity were identified by comparing the different culture systems. Furthermore, we demonstrated that the cooperation of NK cells with tumor-reactive T cells or with NY-ESO-1-specific TCR-T cells further enhanced tumors lysis, especially against tumors with downregulated HLA-I expression. The advantages of HLA-mismatch and non-rejection by other allogeneic immune cells demonstrated the potential of “off-the-shelf” NK cells with the capacity to target tumors for immunotherapy. Our results indicate that the combination strategy based on T cell and allogeneic NK cell immunotherapy might have potential for overcoming the barrier of immune incompetence caused by HLA-I downregulation. |
| first_indexed | 2024-03-11T10:05:44Z |
| format | Article |
| id | doaj.art-44b58688ff174c748b5ec1f2e3bebce0 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T10:05:44Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-44b58688ff174c748b5ec1f2e3bebce02023-11-16T15:03:40ZengMDPI AGCancers2072-66942022-12-0115125110.3390/cancers15010251Combination of Expanded Allogeneic NK Cells and T Cell-Based Immunotherapy Exert Enhanced Antitumor EffectsXiao Wang0Xuejiao Yang1Yueping Wang2Yunshuo Chen3Ying Yang4Siqi Shang5Wenbo Wang6Yueying Wang7Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaInstitute of Interdisciplinary Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, ChinaShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDepartment of Oncology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaShanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaImmunotherapies based on immune checkpoint blockade, neoantigen-reactive tumor-infiltrating lymphocytes and T cell receptor-engineered T cells (TCR-T) have achieved favorable clinical outcomes in tumor treatment. However, sustained immune response and tumor regression have been observed only in a few patients due to immune escape. Natural killer (NK) cells can mediate direct tumor lysis and target cancer cells with low or no expression of human leukocyte antigen class I (HLA-I) that are no longer recognized by T cells during immune escape. Therefore, the combination of T cell-based immunotherapy and NK cell therapy is a promising strategy for improving antitumor response and response rate. However, allogeneic NK cells for adoptive cell therapy have been limited by both the required cell number and quality. Here, we developed an efficient manufacturing system that relies on genetically modified K562 cells for the expansion of high-quality NK cells derived from peripheral blood mononuclear cells. NK cells with the optimal expansion and activity were identified by comparing the different culture systems. Furthermore, we demonstrated that the cooperation of NK cells with tumor-reactive T cells or with NY-ESO-1-specific TCR-T cells further enhanced tumors lysis, especially against tumors with downregulated HLA-I expression. The advantages of HLA-mismatch and non-rejection by other allogeneic immune cells demonstrated the potential of “off-the-shelf” NK cells with the capacity to target tumors for immunotherapy. Our results indicate that the combination strategy based on T cell and allogeneic NK cell immunotherapy might have potential for overcoming the barrier of immune incompetence caused by HLA-I downregulation.https://www.mdpi.com/2072-6694/15/1/251natural killer cellstumor-reactive T cellsT cell receptor-engineered T cellshuman leukocyte antigencombination immunotherapy |
| spellingShingle | Xiao Wang Xuejiao Yang Yueping Wang Yunshuo Chen Ying Yang Siqi Shang Wenbo Wang Yueying Wang Combination of Expanded Allogeneic NK Cells and T Cell-Based Immunotherapy Exert Enhanced Antitumor Effects Cancers natural killer cells tumor-reactive T cells T cell receptor-engineered T cells human leukocyte antigen combination immunotherapy |
| title | Combination of Expanded Allogeneic NK Cells and T Cell-Based Immunotherapy Exert Enhanced Antitumor Effects |
| title_full | Combination of Expanded Allogeneic NK Cells and T Cell-Based Immunotherapy Exert Enhanced Antitumor Effects |
| title_fullStr | Combination of Expanded Allogeneic NK Cells and T Cell-Based Immunotherapy Exert Enhanced Antitumor Effects |
| title_full_unstemmed | Combination of Expanded Allogeneic NK Cells and T Cell-Based Immunotherapy Exert Enhanced Antitumor Effects |
| title_short | Combination of Expanded Allogeneic NK Cells and T Cell-Based Immunotherapy Exert Enhanced Antitumor Effects |
| title_sort | combination of expanded allogeneic nk cells and t cell based immunotherapy exert enhanced antitumor effects |
| topic | natural killer cells tumor-reactive T cells T cell receptor-engineered T cells human leukocyte antigen combination immunotherapy |
| url | https://www.mdpi.com/2072-6694/15/1/251 |
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