Enhanced Delivery of Rituximab Into Brain and Lymph Nodes Using Timed-Release Nanocapsules in Non-Human Primates
Tumor metastasis into the central nervous system (CNS) and lymph nodes (LNs) is a major obstacle for effective therapies. Therapeutic monoclonal antibodies (mAb) have revolutionized tumor treatment; however, their efficacy for treating metastatic tumors-particularly, CNS and LN metastases-is poor du...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.03132/full |
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| author | Meng Qin Meng Qin Lan Wang Lan Wang Di Wu Christopher K. Williams Duo Xu Emiko Kranz Emiko Kranz Qi Guo Qi Guo Jiaoqiong Guan Harry V. Vinters YooJin Lee YooJin Lee Yiming Xie Yiming Xie Yun Luo Guibo Sun Xiaobo Sun Zhanlong He Yunfeng Lu Masakazu Kamata Masakazu Kamata Jing Wen Jing Wen Irvin S. Y. Chen Irvin S. Y. Chen |
| author_facet | Meng Qin Meng Qin Lan Wang Lan Wang Di Wu Christopher K. Williams Duo Xu Emiko Kranz Emiko Kranz Qi Guo Qi Guo Jiaoqiong Guan Harry V. Vinters YooJin Lee YooJin Lee Yiming Xie Yiming Xie Yun Luo Guibo Sun Xiaobo Sun Zhanlong He Yunfeng Lu Masakazu Kamata Masakazu Kamata Jing Wen Jing Wen Irvin S. Y. Chen Irvin S. Y. Chen |
| author_sort | Meng Qin |
| collection | DOAJ |
| description | Tumor metastasis into the central nervous system (CNS) and lymph nodes (LNs) is a major obstacle for effective therapies. Therapeutic monoclonal antibodies (mAb) have revolutionized tumor treatment; however, their efficacy for treating metastatic tumors-particularly, CNS and LN metastases-is poor due to inefficient penetration into the CNS and LNs following intravenous injection. We recently reported an effective delivery of mAb to the CNS by encapsulating the anti-CD20 mAb rituximab (RTX) within a thin shell of polymer that contains the analogs of choline and acetylcholine receptors. This encapsulated RTX, denoted as n-RTX, eliminated lymphoma cells systemically in a xenografted humanized mouse model using an immunodeficient mouse as a recipient of human hematopoietic stem/progenitor cells and fetal thymus more effectively than native RTX; importantly, n-RTX showed notable anti-tumor effect on CNS metastases which is unable to show by native RTX. As an important step toward future clinical translation of this technology, we further analyzed the properties of n-RTX in immunocompetent animals, rats, and non-human primates (NHPs). Our results show that a single intravenous injection of n-RTX resulted in 10-fold greater levels in the CNS and 2-3-fold greater levels in the LNs of RTX, respectively, than the injection of native RTX in both rats and NHPs. In addition, we demonstrate the enhanced delivery and efficient B-cell depletion in lymphoid organs of NHPs with n-RTX. Moreover, detailed hematological analysis and liver enzyme activity tests indicate n-RTX treatment is safe in NHPs. As this nanocapsule platform can be universally applied to other therapeutic mAbs, it holds great promise for extending mAb therapy to poorly accessible body compartments. |
| first_indexed | 2024-12-20T10:52:35Z |
| format | Article |
| id | doaj.art-12d7f398dcad4f9bb9c0eeee72da161b |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T10:52:35Z |
| publishDate | 2020-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-12d7f398dcad4f9bb9c0eeee72da161b2022-12-21T19:43:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-01-011010.3389/fimmu.2019.03132507004Enhanced Delivery of Rituximab Into Brain and Lymph Nodes Using Timed-Release Nanocapsules in Non-Human PrimatesMeng Qin0Meng Qin1Lan Wang2Lan Wang3Di Wu4Christopher K. Williams5Duo Xu6Emiko Kranz7Emiko Kranz8Qi Guo9Qi Guo10Jiaoqiong Guan11Harry V. Vinters12YooJin Lee13YooJin Lee14Yiming Xie15Yiming Xie16Yun Luo17Guibo Sun18Xiaobo Sun19Zhanlong He20Yunfeng Lu21Masakazu Kamata22Masakazu Kamata23Jing Wen24Jing Wen25Irvin S. Y. Chen26Irvin S. Y. Chen27Department of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, United StatesUCLA AIDS Institute, Los Angeles, CA, United StatesDepartment of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, United StatesUCLA AIDS Institute, Los Angeles, CA, United StatesDepartment of Chemical and Biomolecular Engineering, School of Engineering, UCLA, Los Angeles, CA, United StatesDepartments of Pathology & Laboratory Medicine (Neuropathology) and Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United StatesDepartment of Chemical and Biomolecular Engineering, School of Engineering, UCLA, Los Angeles, CA, United StatesUCLA AIDS Institute, Los Angeles, CA, United StatesDivision of Hematology-Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United StatesUCLA AIDS Institute, Los Angeles, CA, United StatesSchool of Nursing, UCLA, Los Angeles, CA, United StatesInstitute of Medical Biology, Peking Union Medical College, Chinese Academy of Medical Sciences, Kunming, ChinaDepartments of Pathology & Laboratory Medicine (Neuropathology) and Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United StatesDepartment of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, United StatesUCLA AIDS Institute, Los Angeles, CA, United StatesDepartment of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, United StatesUCLA AIDS Institute, Los Angeles, CA, United StatesInstitute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaInstitute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaInstitute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, ChinaInstitute of Medical Biology, Peking Union Medical College, Chinese Academy of Medical Sciences, Kunming, ChinaDepartment of Chemical and Biomolecular Engineering, School of Engineering, UCLA, Los Angeles, CA, United StatesUCLA AIDS Institute, Los Angeles, CA, United StatesDivision of Hematology-Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA, United StatesDepartment of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, United StatesUCLA AIDS Institute, Los Angeles, CA, United StatesDepartment of Microbiology, Immunology and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, United StatesUCLA AIDS Institute, Los Angeles, CA, United StatesTumor metastasis into the central nervous system (CNS) and lymph nodes (LNs) is a major obstacle for effective therapies. Therapeutic monoclonal antibodies (mAb) have revolutionized tumor treatment; however, their efficacy for treating metastatic tumors-particularly, CNS and LN metastases-is poor due to inefficient penetration into the CNS and LNs following intravenous injection. We recently reported an effective delivery of mAb to the CNS by encapsulating the anti-CD20 mAb rituximab (RTX) within a thin shell of polymer that contains the analogs of choline and acetylcholine receptors. This encapsulated RTX, denoted as n-RTX, eliminated lymphoma cells systemically in a xenografted humanized mouse model using an immunodeficient mouse as a recipient of human hematopoietic stem/progenitor cells and fetal thymus more effectively than native RTX; importantly, n-RTX showed notable anti-tumor effect on CNS metastases which is unable to show by native RTX. As an important step toward future clinical translation of this technology, we further analyzed the properties of n-RTX in immunocompetent animals, rats, and non-human primates (NHPs). Our results show that a single intravenous injection of n-RTX resulted in 10-fold greater levels in the CNS and 2-3-fold greater levels in the LNs of RTX, respectively, than the injection of native RTX in both rats and NHPs. In addition, we demonstrate the enhanced delivery and efficient B-cell depletion in lymphoid organs of NHPs with n-RTX. Moreover, detailed hematological analysis and liver enzyme activity tests indicate n-RTX treatment is safe in NHPs. As this nanocapsule platform can be universally applied to other therapeutic mAbs, it holds great promise for extending mAb therapy to poorly accessible body compartments.https://www.frontiersin.org/article/10.3389/fimmu.2019.03132/fullmonoclonal antibodycentral nervous system deliveryLNs deliverynon-human primatenanocapsules |
| spellingShingle | Meng Qin Meng Qin Lan Wang Lan Wang Di Wu Christopher K. Williams Duo Xu Emiko Kranz Emiko Kranz Qi Guo Qi Guo Jiaoqiong Guan Harry V. Vinters YooJin Lee YooJin Lee Yiming Xie Yiming Xie Yun Luo Guibo Sun Xiaobo Sun Zhanlong He Yunfeng Lu Masakazu Kamata Masakazu Kamata Jing Wen Jing Wen Irvin S. Y. Chen Irvin S. Y. Chen Enhanced Delivery of Rituximab Into Brain and Lymph Nodes Using Timed-Release Nanocapsules in Non-Human Primates Frontiers in Immunology monoclonal antibody central nervous system delivery LNs delivery non-human primate nanocapsules |
| title | Enhanced Delivery of Rituximab Into Brain and Lymph Nodes Using Timed-Release Nanocapsules in Non-Human Primates |
| title_full | Enhanced Delivery of Rituximab Into Brain and Lymph Nodes Using Timed-Release Nanocapsules in Non-Human Primates |
| title_fullStr | Enhanced Delivery of Rituximab Into Brain and Lymph Nodes Using Timed-Release Nanocapsules in Non-Human Primates |
| title_full_unstemmed | Enhanced Delivery of Rituximab Into Brain and Lymph Nodes Using Timed-Release Nanocapsules in Non-Human Primates |
| title_short | Enhanced Delivery of Rituximab Into Brain and Lymph Nodes Using Timed-Release Nanocapsules in Non-Human Primates |
| title_sort | enhanced delivery of rituximab into brain and lymph nodes using timed release nanocapsules in non human primates |
| topic | monoclonal antibody central nervous system delivery LNs delivery non-human primate nanocapsules |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.03132/full |
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