Leukemia’s Next Top Model? Syngeneic Models to Advance Adoptive Cellular Therapy
In recent years, there has been an emphasis on harnessing the immune system for therapeutic interventions. Adoptive cell therapies (ACT) have emerged as an effective option for B-cell derived hematological malignancies. Despite remarkable successes with ACT, immune dysregulation and the leukemia mic...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.867103/full |
| _version_ | 1819175229939777536 |
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| author | Jaquelyn T. Zoine Sarah E. Moore Sarah E. Moore M. Paulina Velasquez |
| author_facet | Jaquelyn T. Zoine Sarah E. Moore Sarah E. Moore M. Paulina Velasquez |
| author_sort | Jaquelyn T. Zoine |
| collection | DOAJ |
| description | In recent years, there has been an emphasis on harnessing the immune system for therapeutic interventions. Adoptive cell therapies (ACT) have emerged as an effective option for B-cell derived hematological malignancies. Despite remarkable successes with ACT, immune dysregulation and the leukemia microenvironment can critically alter clinical responses. Therefore, preclinical modeling can contribute to the advancement of ACT for leukemias. Human xenografts, the current mainstay of ACT in vivo models, cannot evaluate the impact of the immunosuppressive leukemia microenvironment on adoptively transferred cells. Syngeneic mouse models utilize murine tumor models and implant them into immunocompetent mice. This provides an alternative model, reducing the need for complicated breeding strategies while maintaining a matched immune system, stromal compartment, and leukemia burden. Syngeneic models that evaluate ACT have analyzed the complexity of cytotoxic T lymphocytes, T cell receptor transgenics, and chimeric antigen receptors. This review examines the immunosuppressive features of the leukemia microenvironment, discusses how preclinical modeling helps predict ACT associated toxicities and dysfunction, and explores publications that have employed syngeneic modeling in ACT studies for the improvement of therapy for leukemias. |
| first_indexed | 2024-12-22T20:51:33Z |
| format | Article |
| id | doaj.art-79389b9622784c2e9583264ff07b59da |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-22T20:51:33Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-79389b9622784c2e9583264ff07b59da2022-12-21T18:13:05ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-03-011310.3389/fimmu.2022.867103867103Leukemia’s Next Top Model? Syngeneic Models to Advance Adoptive Cellular TherapyJaquelyn T. Zoine0Sarah E. Moore1Sarah E. Moore2M. Paulina Velasquez3Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children’s Research Hospital, Memphis, TN, United StatesDepartment of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children’s Research Hospital, Memphis, TN, United StatesGraduate School of Biomedical Sciences, St. Jude Children’s Research Hospital, Memphis, TN, United StatesDepartment of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children’s Research Hospital, Memphis, TN, United StatesIn recent years, there has been an emphasis on harnessing the immune system for therapeutic interventions. Adoptive cell therapies (ACT) have emerged as an effective option for B-cell derived hematological malignancies. Despite remarkable successes with ACT, immune dysregulation and the leukemia microenvironment can critically alter clinical responses. Therefore, preclinical modeling can contribute to the advancement of ACT for leukemias. Human xenografts, the current mainstay of ACT in vivo models, cannot evaluate the impact of the immunosuppressive leukemia microenvironment on adoptively transferred cells. Syngeneic mouse models utilize murine tumor models and implant them into immunocompetent mice. This provides an alternative model, reducing the need for complicated breeding strategies while maintaining a matched immune system, stromal compartment, and leukemia burden. Syngeneic models that evaluate ACT have analyzed the complexity of cytotoxic T lymphocytes, T cell receptor transgenics, and chimeric antigen receptors. This review examines the immunosuppressive features of the leukemia microenvironment, discusses how preclinical modeling helps predict ACT associated toxicities and dysfunction, and explores publications that have employed syngeneic modeling in ACT studies for the improvement of therapy for leukemias.https://www.frontiersin.org/articles/10.3389/fimmu.2022.867103/fulladoptive cell immunotherapyleukemiasyngeneic animal modelleukemia microenvironmentcell therapy |
| spellingShingle | Jaquelyn T. Zoine Sarah E. Moore Sarah E. Moore M. Paulina Velasquez Leukemia’s Next Top Model? Syngeneic Models to Advance Adoptive Cellular Therapy Frontiers in Immunology adoptive cell immunotherapy leukemia syngeneic animal model leukemia microenvironment cell therapy |
| title | Leukemia’s Next Top Model? Syngeneic Models to Advance Adoptive Cellular Therapy |
| title_full | Leukemia’s Next Top Model? Syngeneic Models to Advance Adoptive Cellular Therapy |
| title_fullStr | Leukemia’s Next Top Model? Syngeneic Models to Advance Adoptive Cellular Therapy |
| title_full_unstemmed | Leukemia’s Next Top Model? Syngeneic Models to Advance Adoptive Cellular Therapy |
| title_short | Leukemia’s Next Top Model? Syngeneic Models to Advance Adoptive Cellular Therapy |
| title_sort | leukemia s next top model syngeneic models to advance adoptive cellular therapy |
| topic | adoptive cell immunotherapy leukemia syngeneic animal model leukemia microenvironment cell therapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.867103/full |
| work_keys_str_mv | AT jaquelyntzoine leukemiasnexttopmodelsyngeneicmodelstoadvanceadoptivecellulartherapy AT sarahemoore leukemiasnexttopmodelsyngeneicmodelstoadvanceadoptivecellulartherapy AT sarahemoore leukemiasnexttopmodelsyngeneicmodelstoadvanceadoptivecellulartherapy AT mpaulinavelasquez leukemiasnexttopmodelsyngeneicmodelstoadvanceadoptivecellulartherapy |