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Published on: May 22, 2020
Fucoidan potentiates CAR NK cell-mediated antitumor efficacy against non-Hodgkin lymphoma via NRF2
Zhenhai Li1, Xuanren Shi2, Fei Wang3
1Department of Hematology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, 518036, China.
Abstract:
Although the potential for synergistic effects between fucoidan (FO) and anticancer drugs has been documented in numerous preclinical studies, FO's potential application in cellular immunotherapy remains largely unexplored. CAR NK cell therapy has emerged as a promising strategy in cancer immunotherapy. In this study, we investigated the role of FO in CAR NK cell therapy for non-Hodgkin lymphoma (NHL). Our findings reveal that FO enhances the functionality of CAR NK cells by augmenting NRF2 activity. FO improved cellular energetic metabolism and increased antioxidant activity of CAR NK cells. Notably, FO-treated CAR NK cells demonstrated enhanced cytotoxicity against NHL cells and elevated cytokine secretion. Additionally, FO prolonged the persistence of CAR NK cells in tissues. Intravenous administration of CD19-CAR NK cells combined with FO effectively eradicated NHL cancer cells in intraperitoneally tumor-bearing mice and significantly extended their survival. These results highlight the supportive role of FO in CAR NK cell-based therapies and suggest its potential as an adjuvant in clinical cellular immunotherapy.
Insights
Fucoidan (FO) enhances CAR NK cell therapy for non-Hodgkin lymphoma by boosting cell function and persistence. This study shows FO as a potential adjuvant for cellular immunotherapy, improving treatment outcomes.
Area of Science:
- Immunology
- Oncology
- Biochemistry
Background:
- Cellular immunotherapy, particularly CAR NK cell therapy, shows promise for cancer treatment.
- Fucoidan (FO) is known for synergistic effects with anticancer drugs, but its role in cellular immunotherapy is unexplored.
- Non-Hodgkin lymphoma (NHL) is a target for novel therapeutic strategies.
Purpose of the Study:
- To investigate the role of fucoidan (FO) in enhancing CAR NK cell therapy for non-Hodgkin lymphoma (NHL).
- To determine if FO can improve the functionality, metabolism, and persistence of CAR NK cells.
Main Methods:
- CAR NK cells were treated with FO in vitro and in vivo.
- NRF2 activity, cellular energetic metabolism, and antioxidant capacity were assessed.
- Cytotoxicity against NHL cells and cytokine secretion were measured.
- Efficacy was evaluated in a mouse model of NHL.
Main Results:
- FO treatment augmented NRF2 activity, improved energetic metabolism, and increased antioxidant capacity in CAR NK cells.
- FO-enhanced CAR NK cells exhibited increased cytotoxicity against NHL cells and elevated cytokine secretion.
- FO prolonged the persistence of CAR NK cells and demonstrated significant efficacy in eradicating NHL in vivo, extending survival.
Conclusions:
- Fucoidan (FO) supports and enhances CAR NK cell therapy for NHL by improving cell function and persistence.
- FO shows potential as an effective adjuvant for clinical cellular immunotherapy strategies.
- These findings open new avenues for leveraging FO in combination cancer therapies.
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