Treatment of aggressive T-cell lymphoma/leukemia with anti-CD4 CAR T cells
T-cell lymphomas are aggressive lymphomas that often resist current therapy options or present with relapsed disease, making the development of more effective treatment regimens clinically important. Previously, we have shown that CD4 CAR can effectively target T-cell malignancies in preclinical stu...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.997482/full |
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| author | Jia Feng Haichan Xu Andrew Cinquina Zehua Wu Wenli Zhang Lihua Sun Qi Chen Lei Tian Le Song Kevin G. Pinz Masayuki Wada Xun Jiang William M. Hanes Yupo Ma Hongyu Zhang |
| author_facet | Jia Feng Haichan Xu Andrew Cinquina Zehua Wu Wenli Zhang Lihua Sun Qi Chen Lei Tian Le Song Kevin G. Pinz Masayuki Wada Xun Jiang William M. Hanes Yupo Ma Hongyu Zhang |
| author_sort | Jia Feng |
| collection | DOAJ |
| description | T-cell lymphomas are aggressive lymphomas that often resist current therapy options or present with relapsed disease, making the development of more effective treatment regimens clinically important. Previously, we have shown that CD4 CAR can effectively target T-cell malignancies in preclinical studies. As IL-15 has been shown to strengthen the anti-tumor response, we have modified CD4 CAR to secrete an IL-15/IL-15sushi complex. These CD4-IL15/IL15sushi CAR T cells and NK92 cells efficiently eliminated CD4+ leukemic cell lines in co-culture assays. Additionally, CD4-IL15/IL15sushi CAR out-performed CD4 CAR in in vivo models, demonstrating a benefit to IL-15/IL-15sushi inclusion. In a Phase I clinical trial, CD4-IL15/IL15sushi CAR T cells were tested for safety in three patients with different T-cell lymphomas. Infusion of CD4-IL15/IL15sushi CAR T cells was well-tolerated by the patients without significant adverse effects and led to the remission of their lymphomas. Additionally, infusion led to the depletion of CD4+ Treg cells and expansion of CD3+CD8+ T cells and NK cells. These results suggest that CD4-IL15/IL15sushi CAR T cells may be a safe and effective treatment for patients with relapsed or refractory T-cell lymphomas, where new treatment options are needed. |
| first_indexed | 2024-12-10T14:51:16Z |
| format | Article |
| id | doaj.art-52eee73e480b4c79872209d7c637ada0 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-10T14:51:16Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-52eee73e480b4c79872209d7c637ada02022-12-22T01:44:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-09-011310.3389/fimmu.2022.997482997482Treatment of aggressive T-cell lymphoma/leukemia with anti-CD4 CAR T cellsJia Feng0Haichan Xu1Andrew Cinquina2Zehua Wu3Wenli Zhang4Lihua Sun5Qi Chen6Lei Tian7Le Song8Kevin G. Pinz9Masayuki Wada10Xun Jiang11William M. Hanes12Yupo Ma13Hongyu Zhang14Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, ChinaDepartment of Hematology, Peking University Shenzhen Hospital, Shenzhen, ChinaiCell Gene Therapeutics LLC, Research & Development Division, Long Island High Technology Incubator, Stony Brook, NY, United StatesDepartment of Hematology, Peking University Shenzhen Hospital, Shenzhen, ChinaDepartment of Hematology, Peking University Shenzhen Hospital, Shenzhen, ChinaDepartment of Hematology, Peking University Shenzhen Hospital, Shenzhen, ChinaDepartment of Hematology, Peking University Shenzhen Hospital, Shenzhen, ChinaDepartment of Hematology, Peking University Third Hospital, Beijing, ChinaDepartment of Nuclear Medicine, Peking University Third Hospital, Beijing, ChinaiCell Gene Therapeutics LLC, Research & Development Division, Long Island High Technology Incubator, Stony Brook, NY, United StatesiCell Gene Therapeutics LLC, Research & Development Division, Long Island High Technology Incubator, Stony Brook, NY, United StatesiCell Gene Therapeutics LLC, Research & Development Division, Long Island High Technology Incubator, Stony Brook, NY, United StatesiCell Gene Therapeutics LLC, Research & Development Division, Long Island High Technology Incubator, Stony Brook, NY, United StatesiCell Gene Therapeutics LLC, Research & Development Division, Long Island High Technology Incubator, Stony Brook, NY, United StatesDepartment of Hematology, Peking University Shenzhen Hospital, Shenzhen, ChinaT-cell lymphomas are aggressive lymphomas that often resist current therapy options or present with relapsed disease, making the development of more effective treatment regimens clinically important. Previously, we have shown that CD4 CAR can effectively target T-cell malignancies in preclinical studies. As IL-15 has been shown to strengthen the anti-tumor response, we have modified CD4 CAR to secrete an IL-15/IL-15sushi complex. These CD4-IL15/IL15sushi CAR T cells and NK92 cells efficiently eliminated CD4+ leukemic cell lines in co-culture assays. Additionally, CD4-IL15/IL15sushi CAR out-performed CD4 CAR in in vivo models, demonstrating a benefit to IL-15/IL-15sushi inclusion. In a Phase I clinical trial, CD4-IL15/IL15sushi CAR T cells were tested for safety in three patients with different T-cell lymphomas. Infusion of CD4-IL15/IL15sushi CAR T cells was well-tolerated by the patients without significant adverse effects and led to the remission of their lymphomas. Additionally, infusion led to the depletion of CD4+ Treg cells and expansion of CD3+CD8+ T cells and NK cells. These results suggest that CD4-IL15/IL15sushi CAR T cells may be a safe and effective treatment for patients with relapsed or refractory T-cell lymphomas, where new treatment options are needed.https://www.frontiersin.org/articles/10.3389/fimmu.2022.997482/fullT-cell lymphomahematopoietic cellsCAR T cellsCD4 CARIL15/IL15sushi |
| spellingShingle | Jia Feng Haichan Xu Andrew Cinquina Zehua Wu Wenli Zhang Lihua Sun Qi Chen Lei Tian Le Song Kevin G. Pinz Masayuki Wada Xun Jiang William M. Hanes Yupo Ma Hongyu Zhang Treatment of aggressive T-cell lymphoma/leukemia with anti-CD4 CAR T cells Frontiers in Immunology T-cell lymphoma hematopoietic cells CAR T cells CD4 CAR IL15/IL15sushi |
| title | Treatment of aggressive T-cell lymphoma/leukemia with anti-CD4 CAR T cells |
| title_full | Treatment of aggressive T-cell lymphoma/leukemia with anti-CD4 CAR T cells |
| title_fullStr | Treatment of aggressive T-cell lymphoma/leukemia with anti-CD4 CAR T cells |
| title_full_unstemmed | Treatment of aggressive T-cell lymphoma/leukemia with anti-CD4 CAR T cells |
| title_short | Treatment of aggressive T-cell lymphoma/leukemia with anti-CD4 CAR T cells |
| title_sort | treatment of aggressive t cell lymphoma leukemia with anti cd4 car t cells |
| topic | T-cell lymphoma hematopoietic cells CAR T cells CD4 CAR IL15/IL15sushi |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.997482/full |
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