Beyond αβ T cells: NK, iNKT, and γδT cell biology in leukemic patients and potential for off-the-shelf adoptive cell therapies for AML
Acute myeloid leukemia (AML) remains an elusive disease to treat, let alone cure, even after highly intensive therapies such as stem cell transplants. Adoptive cell therapeutic strategies based on conventional alpha beta (αβ)T cells are an active area of research in myeloid neoplasms given their rem...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1202950/full |
| _version_ | 1797742162720325632 |
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| author | Andrew Kent Andrew Kent Andrew Kent Lyndsey S. Crump Eduardo Davila Eduardo Davila Eduardo Davila Eduardo Davila |
| author_facet | Andrew Kent Andrew Kent Andrew Kent Lyndsey S. Crump Eduardo Davila Eduardo Davila Eduardo Davila Eduardo Davila |
| author_sort | Andrew Kent |
| collection | DOAJ |
| description | Acute myeloid leukemia (AML) remains an elusive disease to treat, let alone cure, even after highly intensive therapies such as stem cell transplants. Adoptive cell therapeutic strategies based on conventional alpha beta (αβ)T cells are an active area of research in myeloid neoplasms given their remarkable success in other hematologic malignancies, particularly B-cell-derived acute lymphoid leukemia, myeloma, and lymphomas. Several limitations have hindered clinical application of adoptive cell therapies in AML including lack of leukemia-specific antigens, on-target-off-leukemic toxicity, immunosuppressive microenvironments, and leukemic stem cell populations elusive to immune recognition and destruction. While there are promising T cell-based therapies including chimeric antigen receptor (CAR)-T designs under development, other cytotoxic lymphocyte cell subsets have unique phenotypes and capabilities that might be of additional benefit in AML treatment. Of particular interest are the natural killer (NK) and unconventional T cells known as invariant natural killer T (iNKT) and gamma delta (γδ) T cells. NK, iNKT, and γδT cells exhibit intrinsic anti-malignant properties, potential for alloreactivity, and human leukocyte-antigen (HLA)-independent function. Here we review the biology of each of these unconventional cytotoxic lymphocyte cell types and compare and contrast their strengths and limitations as the basis for adoptive cell therapies for AML. |
| first_indexed | 2024-03-12T14:37:02Z |
| format | Article |
| id | doaj.art-37d6be280ac44d4986a65ca4e2b15895 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T14:37:02Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-37d6be280ac44d4986a65ca4e2b158952023-08-17T04:22:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-08-011410.3389/fimmu.2023.12029501202950Beyond αβ T cells: NK, iNKT, and γδT cell biology in leukemic patients and potential for off-the-shelf adoptive cell therapies for AMLAndrew Kent0Andrew Kent1Andrew Kent2Lyndsey S. Crump3Eduardo Davila4Eduardo Davila5Eduardo Davila6Eduardo Davila7Division of Medical Oncology, Department of Medicine, University of Colorado, Aurora, CO, United StatesHuman Immunology and Immunotherapy Initiative, University of Colorado, Aurora, CO, United StatesDepartment of Medicine, University of Colorado Comprehensive Cancer Center, Aurora, CO, United StatesTrAMPoline Pharma, Inc., Aurora, CO, United StatesDivision of Medical Oncology, Department of Medicine, University of Colorado, Aurora, CO, United StatesHuman Immunology and Immunotherapy Initiative, University of Colorado, Aurora, CO, United StatesDepartment of Medicine, University of Colorado Comprehensive Cancer Center, Aurora, CO, United StatesDepartment of Medicine, University of Colorado, Aurora, CO, United StatesAcute myeloid leukemia (AML) remains an elusive disease to treat, let alone cure, even after highly intensive therapies such as stem cell transplants. Adoptive cell therapeutic strategies based on conventional alpha beta (αβ)T cells are an active area of research in myeloid neoplasms given their remarkable success in other hematologic malignancies, particularly B-cell-derived acute lymphoid leukemia, myeloma, and lymphomas. Several limitations have hindered clinical application of adoptive cell therapies in AML including lack of leukemia-specific antigens, on-target-off-leukemic toxicity, immunosuppressive microenvironments, and leukemic stem cell populations elusive to immune recognition and destruction. While there are promising T cell-based therapies including chimeric antigen receptor (CAR)-T designs under development, other cytotoxic lymphocyte cell subsets have unique phenotypes and capabilities that might be of additional benefit in AML treatment. Of particular interest are the natural killer (NK) and unconventional T cells known as invariant natural killer T (iNKT) and gamma delta (γδ) T cells. NK, iNKT, and γδT cells exhibit intrinsic anti-malignant properties, potential for alloreactivity, and human leukocyte-antigen (HLA)-independent function. Here we review the biology of each of these unconventional cytotoxic lymphocyte cell types and compare and contrast their strengths and limitations as the basis for adoptive cell therapies for AML.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1202950/fullNK celliNKT cellgdT celladoptive cell therapyacute myeloid leukemiaimmune cell engineering |
| spellingShingle | Andrew Kent Andrew Kent Andrew Kent Lyndsey S. Crump Eduardo Davila Eduardo Davila Eduardo Davila Eduardo Davila Beyond αβ T cells: NK, iNKT, and γδT cell biology in leukemic patients and potential for off-the-shelf adoptive cell therapies for AML Frontiers in Immunology NK cell iNKT cell gdT cell adoptive cell therapy acute myeloid leukemia immune cell engineering |
| title | Beyond αβ T cells: NK, iNKT, and γδT cell biology in leukemic patients and potential for off-the-shelf adoptive cell therapies for AML |
| title_full | Beyond αβ T cells: NK, iNKT, and γδT cell biology in leukemic patients and potential for off-the-shelf adoptive cell therapies for AML |
| title_fullStr | Beyond αβ T cells: NK, iNKT, and γδT cell biology in leukemic patients and potential for off-the-shelf adoptive cell therapies for AML |
| title_full_unstemmed | Beyond αβ T cells: NK, iNKT, and γδT cell biology in leukemic patients and potential for off-the-shelf adoptive cell therapies for AML |
| title_short | Beyond αβ T cells: NK, iNKT, and γδT cell biology in leukemic patients and potential for off-the-shelf adoptive cell therapies for AML |
| title_sort | beyond αβ t cells nk inkt and γδt cell biology in leukemic patients and potential for off the shelf adoptive cell therapies for aml |
| topic | NK cell iNKT cell gdT cell adoptive cell therapy acute myeloid leukemia immune cell engineering |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1202950/full |
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