Loading of CAR‐T cells with magnetic nanoparticles for controlled targeting suppresses inflammatory cytokine release and switches tumor cell death mechanism
Abstract Therapies against hematological malignancies using chimeric antigen receptors (CAR)‐T cells have shown great potential; however, therapeutic success in solid tumors has been constrained due to limited tumor trafficking and infiltration, as well as the scarcity of cancer‐specific solid tumor...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-01-01
|
| Series: | MedComm |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mco2.70039 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832594222091337728 |
|---|---|
| author | Felix Pfister Lucas R. Carnell Lisa Löffler Philipp Boosz Niels Schaft Jan Dörrie René Stein Malte Lenz Erdmann Spiecker Christian M. Huber Sami Haddadin Carola Berking Christoph Alexiou Christina Janko |
| author_facet | Felix Pfister Lucas R. Carnell Lisa Löffler Philipp Boosz Niels Schaft Jan Dörrie René Stein Malte Lenz Erdmann Spiecker Christian M. Huber Sami Haddadin Carola Berking Christoph Alexiou Christina Janko |
| author_sort | Felix Pfister |
| collection | DOAJ |
| description | Abstract Therapies against hematological malignancies using chimeric antigen receptors (CAR)‐T cells have shown great potential; however, therapeutic success in solid tumors has been constrained due to limited tumor trafficking and infiltration, as well as the scarcity of cancer‐specific solid tumor antigens. Therefore, the enrichment of tumor‐antigen specific CAR‐T cells in the desired region is critical for improving therapy efficacy and reducing systemic on‐target/off‐tumor side effects. Here, we functionalized human CAR‐T cells with superparamagnetic iron oxide nanoparticles (SPIONs), making them magnetically controllable for site‐directed targeting. SPION‐loaded CAR‐T cells maintained their specific cytolytic capacity against melanoma cells expressing the CAR‐specific antigen chondroitin sulfate proteoglycan (CSPG4). Importantly, SPIONs suppressed cytokine release in the loaded CAR‐T cells, shifting the cell death phenotype in the tumor cells from pyroptosis to apoptosis. Furthermore, SPION‐loaded CAR‐T cells could be enriched in a dynamic flow model through an external magnetic field and be detected in MRI. These results demonstrate that lytic cytotoxicity is retained after SPION‐functionalization and provides a basis for future site‐specific immunotherapies against solid tumors with reduced systemic adverse side effects. |
| format | Article |
| id | doaj-art-892c3e4229ed41bf839943f5ae86f53e |
| institution | Kabale University |
| issn | 2688-2663 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj-art-892c3e4229ed41bf839943f5ae86f53e2025-01-20T01:45:44ZengWileyMedComm2688-26632025-01-0161n/an/a10.1002/mco2.70039Loading of CAR‐T cells with magnetic nanoparticles for controlled targeting suppresses inflammatory cytokine release and switches tumor cell death mechanismFelix Pfister0Lucas R. Carnell1Lisa Löffler2Philipp Boosz3Niels Schaft4Jan Dörrie5René Stein6Malte Lenz7Erdmann Spiecker8Christian M. Huber9Sami Haddadin10Carola Berking11Christoph Alexiou12Christina Janko13Department of Otorhinolaryngology Head and Neck Surgery Section of Experimental Oncology and Nanomedicine (SEON) Else Kröner‐Fresenius‐Stiftung Professorship Universitätsklinikum Erlangen Erlangen GermanyDepartment of Otorhinolaryngology Head and Neck Surgery Section of Experimental Oncology and Nanomedicine (SEON) Else Kröner‐Fresenius‐Stiftung Professorship Universitätsklinikum Erlangen Erlangen GermanyDepartment of Otorhinolaryngology Head and Neck Surgery Section of Experimental Oncology and Nanomedicine (SEON) Else Kröner‐Fresenius‐Stiftung Professorship Universitätsklinikum Erlangen Erlangen GermanyDepartment of Otorhinolaryngology Head and Neck Surgery Section of Experimental Oncology and Nanomedicine (SEON) Else Kröner‐Fresenius‐Stiftung Professorship Universitätsklinikum Erlangen Erlangen GermanyFriedrich‐Alexander‐Universität Erlangen‐Nürnberg (FAU) Erlangen GermanyFriedrich‐Alexander‐Universität Erlangen‐Nürnberg (FAU) Erlangen GermanyDepartment of Otorhinolaryngology Head and Neck Surgery Section of Experimental Oncology and Nanomedicine (SEON) Else Kröner‐Fresenius‐Stiftung Professorship Universitätsklinikum Erlangen Erlangen GermanyInstitute of Micro‐ and Nanostructure Research & Center for Nanoanalysis and Electron Microscopy Interdisciplinary Center for Nanostructured Films Friedrich‐Alexander‐University Erlangen Erlangen GermanyInstitute of Micro‐ and Nanostructure Research & Center for Nanoanalysis and Electron Microscopy Interdisciplinary Center for Nanostructured Films Friedrich‐Alexander‐University Erlangen Erlangen GermanyDepartment of Otorhinolaryngology Head and Neck Surgery Section of Experimental Oncology and Nanomedicine (SEON) Else Kröner‐Fresenius‐Stiftung Professorship Universitätsklinikum Erlangen Erlangen GermanyChair of Robotics Science and Systems Intelligence Munich Institute of Robotics and Machine Intelligence (MIRMI), TUM School of Computation, Information and Technology Technical University of Munich Munich GermanyFriedrich‐Alexander‐Universität Erlangen‐Nürnberg (FAU) Erlangen GermanyDepartment of Otorhinolaryngology Head and Neck Surgery Section of Experimental Oncology and Nanomedicine (SEON) Else Kröner‐Fresenius‐Stiftung Professorship Universitätsklinikum Erlangen Erlangen GermanyDepartment of Otorhinolaryngology Head and Neck Surgery Section of Experimental Oncology and Nanomedicine (SEON) Else Kröner‐Fresenius‐Stiftung Professorship Universitätsklinikum Erlangen Erlangen GermanyAbstract Therapies against hematological malignancies using chimeric antigen receptors (CAR)‐T cells have shown great potential; however, therapeutic success in solid tumors has been constrained due to limited tumor trafficking and infiltration, as well as the scarcity of cancer‐specific solid tumor antigens. Therefore, the enrichment of tumor‐antigen specific CAR‐T cells in the desired region is critical for improving therapy efficacy and reducing systemic on‐target/off‐tumor side effects. Here, we functionalized human CAR‐T cells with superparamagnetic iron oxide nanoparticles (SPIONs), making them magnetically controllable for site‐directed targeting. SPION‐loaded CAR‐T cells maintained their specific cytolytic capacity against melanoma cells expressing the CAR‐specific antigen chondroitin sulfate proteoglycan (CSPG4). Importantly, SPIONs suppressed cytokine release in the loaded CAR‐T cells, shifting the cell death phenotype in the tumor cells from pyroptosis to apoptosis. Furthermore, SPION‐loaded CAR‐T cells could be enriched in a dynamic flow model through an external magnetic field and be detected in MRI. These results demonstrate that lytic cytotoxicity is retained after SPION‐functionalization and provides a basis for future site‐specific immunotherapies against solid tumors with reduced systemic adverse side effects.https://doi.org/10.1002/mco2.70039adoptive T cell therapycancerCAR‐T cellmagnetic cell targetingpyroptosissuperparamagnetic iron oxide nanoparticles (SPIONs) |
| spellingShingle | Felix Pfister Lucas R. Carnell Lisa Löffler Philipp Boosz Niels Schaft Jan Dörrie René Stein Malte Lenz Erdmann Spiecker Christian M. Huber Sami Haddadin Carola Berking Christoph Alexiou Christina Janko Loading of CAR‐T cells with magnetic nanoparticles for controlled targeting suppresses inflammatory cytokine release and switches tumor cell death mechanism MedComm adoptive T cell therapy cancer CAR‐T cell magnetic cell targeting pyroptosis superparamagnetic iron oxide nanoparticles (SPIONs) |
| title | Loading of CAR‐T cells with magnetic nanoparticles for controlled targeting suppresses inflammatory cytokine release and switches tumor cell death mechanism |
| title_full | Loading of CAR‐T cells with magnetic nanoparticles for controlled targeting suppresses inflammatory cytokine release and switches tumor cell death mechanism |
| title_fullStr | Loading of CAR‐T cells with magnetic nanoparticles for controlled targeting suppresses inflammatory cytokine release and switches tumor cell death mechanism |
| title_full_unstemmed | Loading of CAR‐T cells with magnetic nanoparticles for controlled targeting suppresses inflammatory cytokine release and switches tumor cell death mechanism |
| title_short | Loading of CAR‐T cells with magnetic nanoparticles for controlled targeting suppresses inflammatory cytokine release and switches tumor cell death mechanism |
| title_sort | loading of car t cells with magnetic nanoparticles for controlled targeting suppresses inflammatory cytokine release and switches tumor cell death mechanism |
| topic | adoptive T cell therapy cancer CAR‐T cell magnetic cell targeting pyroptosis superparamagnetic iron oxide nanoparticles (SPIONs) |
| url | https://doi.org/10.1002/mco2.70039 |
| work_keys_str_mv | AT felixpfister loadingofcartcellswithmagneticnanoparticlesforcontrolledtargetingsuppressesinflammatorycytokinereleaseandswitchestumorcelldeathmechanism AT lucasrcarnell loadingofcartcellswithmagneticnanoparticlesforcontrolledtargetingsuppressesinflammatorycytokinereleaseandswitchestumorcelldeathmechanism AT lisaloffler loadingofcartcellswithmagneticnanoparticlesforcontrolledtargetingsuppressesinflammatorycytokinereleaseandswitchestumorcelldeathmechanism AT philippboosz loadingofcartcellswithmagneticnanoparticlesforcontrolledtargetingsuppressesinflammatorycytokinereleaseandswitchestumorcelldeathmechanism AT nielsschaft loadingofcartcellswithmagneticnanoparticlesforcontrolledtargetingsuppressesinflammatorycytokinereleaseandswitchestumorcelldeathmechanism AT jandorrie loadingofcartcellswithmagneticnanoparticlesforcontrolledtargetingsuppressesinflammatorycytokinereleaseandswitchestumorcelldeathmechanism AT renestein loadingofcartcellswithmagneticnanoparticlesforcontrolledtargetingsuppressesinflammatorycytokinereleaseandswitchestumorcelldeathmechanism AT maltelenz loadingofcartcellswithmagneticnanoparticlesforcontrolledtargetingsuppressesinflammatorycytokinereleaseandswitchestumorcelldeathmechanism AT erdmannspiecker loadingofcartcellswithmagneticnanoparticlesforcontrolledtargetingsuppressesinflammatorycytokinereleaseandswitchestumorcelldeathmechanism AT christianmhuber loadingofcartcellswithmagneticnanoparticlesforcontrolledtargetingsuppressesinflammatorycytokinereleaseandswitchestumorcelldeathmechanism AT samihaddadin loadingofcartcellswithmagneticnanoparticlesforcontrolledtargetingsuppressesinflammatorycytokinereleaseandswitchestumorcelldeathmechanism AT carolaberking loadingofcartcellswithmagneticnanoparticlesforcontrolledtargetingsuppressesinflammatorycytokinereleaseandswitchestumorcelldeathmechanism AT christophalexiou loadingofcartcellswithmagneticnanoparticlesforcontrolledtargetingsuppressesinflammatorycytokinereleaseandswitchestumorcelldeathmechanism AT christinajanko loadingofcartcellswithmagneticnanoparticlesforcontrolledtargetingsuppressesinflammatorycytokinereleaseandswitchestumorcelldeathmechanism |