Building a Better Defense: Expanding and Improving Natural Killer Cells for Adoptive Cell Therapy
Natural killer (NK) cells have gained attention as a promising adoptive cell therapy platform for their potential to improve cancer treatments. NK cells offer distinct advantages over T-cells, including major histocompatibility complex class I (MHC-I)-independent tumor recognition and low risk of to...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-03-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/13/5/451 |
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| author | Andreia Maia Mubin Tarannum Joana R. Lérias Sara Piccinelli Luis Miguel Borrego Markus Maeurer Rizwan Romee Mireia Castillo-Martin |
| author_facet | Andreia Maia Mubin Tarannum Joana R. Lérias Sara Piccinelli Luis Miguel Borrego Markus Maeurer Rizwan Romee Mireia Castillo-Martin |
| author_sort | Andreia Maia |
| collection | DOAJ |
| description | Natural killer (NK) cells have gained attention as a promising adoptive cell therapy platform for their potential to improve cancer treatments. NK cells offer distinct advantages over T-cells, including major histocompatibility complex class I (MHC-I)-independent tumor recognition and low risk of toxicity, even in an allogeneic setting. Despite this tremendous potential, challenges persist, such as limited <i>in vivo</i> persistence, reduced tumor infiltration, and low absolute NK cell numbers. This review outlines several strategies aiming to overcome these challenges. The developed strategies include optimizing NK cell expansion methods and improving NK cell antitumor responses by cytokine stimulation and genetic manipulations. Using K562 cells expressing membrane IL-15 or IL-21 with or without additional activating ligands like 4-1BBL allows “massive” NK cell expansion and makes multiple cell dosing and “off-the-shelf” efforts feasible. Further improvements in NK cell function can be reached by inducing memory-like NK cells, developing chimeric antigen receptor (CAR)-NK cells, or isolating NK-cell-based tumor-infiltrating lymphocytes (TILs). Memory-like NK cells demonstrate higher <i>in vivo</i> persistence and cytotoxicity, with early clinical trials demonstrating safety and promising efficacy. Recent trials using CAR-NK cells have also demonstrated a lack of any major toxicity, including cytokine release syndrome, and, yet, promising clinical activity. Recent data support that the presence of TIL-NK cells is associated with improved overall patient survival in different types of solid tumors such as head and neck, colorectal, breast, and gastric carcinomas, among the most significant. In conclusion, this review presents insights into the diverse strategies available for NK cell expansion, including the roles played by various cytokines, feeder cells, and culture material in influencing the activation phenotype, telomere length, and cytotoxic potential of expanded NK cells. Notably, genetically modified K562 cells have demonstrated significant efficacy in promoting NK cell expansion. Furthermore, culturing NK cells with IL-2 and IL-15 has been shown to improve expansion rates, while the presence of IL-12 and IL-21 has been linked to enhanced cytotoxic function. Overall, this review provides an overview of NK cell expansion methodologies, highlighting the current landscape of clinical trials and the key advancements to enhance NK-cell-based adoptive cell therapy. |
| first_indexed | 2024-04-25T00:32:56Z |
| format | Article |
| id | doaj.art-0e62f82e51834b4986099cbf9c5395be |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-04-25T00:32:56Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-0e62f82e51834b4986099cbf9c5395be2024-03-12T16:41:46ZengMDPI AGCells2073-44092024-03-0113545110.3390/cells13050451Building a Better Defense: Expanding and Improving Natural Killer Cells for Adoptive Cell TherapyAndreia Maia0Mubin Tarannum1Joana R. Lérias2Sara Piccinelli3Luis Miguel Borrego4Markus Maeurer5Rizwan Romee6Mireia Castillo-Martin7Molecular and Experimental Pathology Laboratory, Champalimaud Centre for the Unknown, Champalimaud Foundation, 1400-038 Lisbon, PortugalNK Cell Gene Manipulation and Therapy Laboratory, Division of Cellular Therapy and Stem Cell Transplant, Dana–Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USAImmunoTherapy/ImmunoSurgery, Champalimaud Centre for the Unknown, Champalimaud Foundation, 1400-038 Lisbon, PortugalNK Cell Gene Manipulation and Therapy Laboratory, Division of Cellular Therapy and Stem Cell Transplant, Dana–Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USAComprehensive Health Research Centre (CHRC), NOVA Medical School, Faculdade de Ciências Médicas (FCM), NOVA University of Lisbon, 1099-085 Lisbon, PortugalImmunoTherapy/ImmunoSurgery, Champalimaud Centre for the Unknown, Champalimaud Foundation, 1400-038 Lisbon, PortugalNK Cell Gene Manipulation and Therapy Laboratory, Division of Cellular Therapy and Stem Cell Transplant, Dana–Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USAMolecular and Experimental Pathology Laboratory, Champalimaud Centre for the Unknown, Champalimaud Foundation, 1400-038 Lisbon, PortugalNatural killer (NK) cells have gained attention as a promising adoptive cell therapy platform for their potential to improve cancer treatments. NK cells offer distinct advantages over T-cells, including major histocompatibility complex class I (MHC-I)-independent tumor recognition and low risk of toxicity, even in an allogeneic setting. Despite this tremendous potential, challenges persist, such as limited <i>in vivo</i> persistence, reduced tumor infiltration, and low absolute NK cell numbers. This review outlines several strategies aiming to overcome these challenges. The developed strategies include optimizing NK cell expansion methods and improving NK cell antitumor responses by cytokine stimulation and genetic manipulations. Using K562 cells expressing membrane IL-15 or IL-21 with or without additional activating ligands like 4-1BBL allows “massive” NK cell expansion and makes multiple cell dosing and “off-the-shelf” efforts feasible. Further improvements in NK cell function can be reached by inducing memory-like NK cells, developing chimeric antigen receptor (CAR)-NK cells, or isolating NK-cell-based tumor-infiltrating lymphocytes (TILs). Memory-like NK cells demonstrate higher <i>in vivo</i> persistence and cytotoxicity, with early clinical trials demonstrating safety and promising efficacy. Recent trials using CAR-NK cells have also demonstrated a lack of any major toxicity, including cytokine release syndrome, and, yet, promising clinical activity. Recent data support that the presence of TIL-NK cells is associated with improved overall patient survival in different types of solid tumors such as head and neck, colorectal, breast, and gastric carcinomas, among the most significant. In conclusion, this review presents insights into the diverse strategies available for NK cell expansion, including the roles played by various cytokines, feeder cells, and culture material in influencing the activation phenotype, telomere length, and cytotoxic potential of expanded NK cells. Notably, genetically modified K562 cells have demonstrated significant efficacy in promoting NK cell expansion. Furthermore, culturing NK cells with IL-2 and IL-15 has been shown to improve expansion rates, while the presence of IL-12 and IL-21 has been linked to enhanced cytotoxic function. Overall, this review provides an overview of NK cell expansion methodologies, highlighting the current landscape of clinical trials and the key advancements to enhance NK-cell-based adoptive cell therapy.https://www.mdpi.com/2073-4409/13/5/451innate immunityNK cellsexpansion methodsadoptive cell therapycytokinesfeeder cells |
| spellingShingle | Andreia Maia Mubin Tarannum Joana R. Lérias Sara Piccinelli Luis Miguel Borrego Markus Maeurer Rizwan Romee Mireia Castillo-Martin Building a Better Defense: Expanding and Improving Natural Killer Cells for Adoptive Cell Therapy Cells innate immunity NK cells expansion methods adoptive cell therapy cytokines feeder cells |
| title | Building a Better Defense: Expanding and Improving Natural Killer Cells for Adoptive Cell Therapy |
| title_full | Building a Better Defense: Expanding and Improving Natural Killer Cells for Adoptive Cell Therapy |
| title_fullStr | Building a Better Defense: Expanding and Improving Natural Killer Cells for Adoptive Cell Therapy |
| title_full_unstemmed | Building a Better Defense: Expanding and Improving Natural Killer Cells for Adoptive Cell Therapy |
| title_short | Building a Better Defense: Expanding and Improving Natural Killer Cells for Adoptive Cell Therapy |
| title_sort | building a better defense expanding and improving natural killer cells for adoptive cell therapy |
| topic | innate immunity NK cells expansion methods adoptive cell therapy cytokines feeder cells |
| url | https://www.mdpi.com/2073-4409/13/5/451 |
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