Immunotherapy against glioblastoma using backpack‐activated neutrophils
Abstract Immune checkpoint inhibitors (ICIs) represent new therapeutic candidates against glioblastoma multiforme (GBM); however, their efficacy is clinically limited due to both local and systemic immunosuppressive environments. Hence, therapeutic approaches that stimulate local and systemic immune...
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| Format: | Article |
| Language: | English |
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Wiley
2025-01-01
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| Series: | Bioengineering & Translational Medicine |
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| Online Access: | https://doi.org/10.1002/btm2.10712 |
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| author | Tatsuya Fukuta Ninad Kumbhojkar Supriya Prakash Suyog Shaha A. Da Silva‐Candal Kyung Soo Park Samir Mitragotri |
| author_facet | Tatsuya Fukuta Ninad Kumbhojkar Supriya Prakash Suyog Shaha A. Da Silva‐Candal Kyung Soo Park Samir Mitragotri |
| author_sort | Tatsuya Fukuta |
| collection | DOAJ |
| description | Abstract Immune checkpoint inhibitors (ICIs) represent new therapeutic candidates against glioblastoma multiforme (GBM); however, their efficacy is clinically limited due to both local and systemic immunosuppressive environments. Hence, therapeutic approaches that stimulate local and systemic immune environments can improve the efficacy of ICIs. Here, we report an adoptive cell therapy employing neutrophils (NE) that are activated via surface attachment of drug‐free disk‐shaped backpacks, termed Cyto‐Adhesive Micro‐Patches (CAMPs) for treating GBM. CAMP‐adhered neutrophils (NE/CAMPs) significantly improved the efficacy of an anti‐PD1 antibody (aPD‐1) in a subcutaneous murine GBM model (GL261). A combination of NE/CAMPs and aPD‐1 completely regressed subcutaneous GL261 tumors in mice. The efficacy of NE/CAMPs against GBM was also tested in an orthotopic GL261 model. Neutrophil's ability to migrate into the brain was not affected by CAMP attachment, and intracerebral NE/CAMP accumulation was observed in mice‐bearing orthotopic GBM. The combination treatment of NE/CAMPs and aPD‐1 activated systemic immune responses mediated by T cells and showed improved therapeutic responses compared with aPD‐1 alone in the orthotopic GBM model. These results suggest that immunomodulation with NE/CAMPs offers a potential approach for the treatment of GBM by combination with ICIs. |
| format | Article |
| id | doaj-art-7fadf0c1a87d4adea18d57267d9076d0 |
| institution | Kabale University |
| issn | 2380-6761 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioengineering & Translational Medicine |
| spelling | doaj-art-7fadf0c1a87d4adea18d57267d9076d02025-01-09T06:19:46ZengWileyBioengineering & Translational Medicine2380-67612025-01-01101n/an/a10.1002/btm2.10712Immunotherapy against glioblastoma using backpack‐activated neutrophilsTatsuya Fukuta0Ninad Kumbhojkar1Supriya Prakash2Suyog Shaha3A. Da Silva‐Candal4Kyung Soo Park5Samir Mitragotri6Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University Boston Massachusetts USAHarvard John A. Paulson School of Engineering and Applied Sciences, Harvard University Boston Massachusetts USAHarvard John A. Paulson School of Engineering and Applied Sciences, Harvard University Boston Massachusetts USAHarvard John A. Paulson School of Engineering and Applied Sciences, Harvard University Boston Massachusetts USAHarvard John A. Paulson School of Engineering and Applied Sciences, Harvard University Boston Massachusetts USAHarvard John A. Paulson School of Engineering and Applied Sciences, Harvard University Boston Massachusetts USAHarvard John A. Paulson School of Engineering and Applied Sciences, Harvard University Boston Massachusetts USAAbstract Immune checkpoint inhibitors (ICIs) represent new therapeutic candidates against glioblastoma multiforme (GBM); however, their efficacy is clinically limited due to both local and systemic immunosuppressive environments. Hence, therapeutic approaches that stimulate local and systemic immune environments can improve the efficacy of ICIs. Here, we report an adoptive cell therapy employing neutrophils (NE) that are activated via surface attachment of drug‐free disk‐shaped backpacks, termed Cyto‐Adhesive Micro‐Patches (CAMPs) for treating GBM. CAMP‐adhered neutrophils (NE/CAMPs) significantly improved the efficacy of an anti‐PD1 antibody (aPD‐1) in a subcutaneous murine GBM model (GL261). A combination of NE/CAMPs and aPD‐1 completely regressed subcutaneous GL261 tumors in mice. The efficacy of NE/CAMPs against GBM was also tested in an orthotopic GL261 model. Neutrophil's ability to migrate into the brain was not affected by CAMP attachment, and intracerebral NE/CAMP accumulation was observed in mice‐bearing orthotopic GBM. The combination treatment of NE/CAMPs and aPD‐1 activated systemic immune responses mediated by T cells and showed improved therapeutic responses compared with aPD‐1 alone in the orthotopic GBM model. These results suggest that immunomodulation with NE/CAMPs offers a potential approach for the treatment of GBM by combination with ICIs.https://doi.org/10.1002/btm2.10712cell therapyglioblastomaimmune checkpoint inhibitorimmunotherapyneutrophils |
| spellingShingle | Tatsuya Fukuta Ninad Kumbhojkar Supriya Prakash Suyog Shaha A. Da Silva‐Candal Kyung Soo Park Samir Mitragotri Immunotherapy against glioblastoma using backpack‐activated neutrophils Bioengineering & Translational Medicine cell therapy glioblastoma immune checkpoint inhibitor immunotherapy neutrophils |
| title | Immunotherapy against glioblastoma using backpack‐activated neutrophils |
| title_full | Immunotherapy against glioblastoma using backpack‐activated neutrophils |
| title_fullStr | Immunotherapy against glioblastoma using backpack‐activated neutrophils |
| title_full_unstemmed | Immunotherapy against glioblastoma using backpack‐activated neutrophils |
| title_short | Immunotherapy against glioblastoma using backpack‐activated neutrophils |
| title_sort | immunotherapy against glioblastoma using backpack activated neutrophils |
| topic | cell therapy glioblastoma immune checkpoint inhibitor immunotherapy neutrophils |
| url | https://doi.org/10.1002/btm2.10712 |
| work_keys_str_mv | AT tatsuyafukuta immunotherapyagainstglioblastomausingbackpackactivatedneutrophils AT ninadkumbhojkar immunotherapyagainstglioblastomausingbackpackactivatedneutrophils AT supriyaprakash immunotherapyagainstglioblastomausingbackpackactivatedneutrophils AT suyogshaha immunotherapyagainstglioblastomausingbackpackactivatedneutrophils AT adasilvacandal immunotherapyagainstglioblastomausingbackpackactivatedneutrophils AT kyungsoopark immunotherapyagainstglioblastomausingbackpackactivatedneutrophils AT samirmitragotri immunotherapyagainstglioblastomausingbackpackactivatedneutrophils |