The Black Hole: CAR T Cell Therapy in AML
Despite exhaustive studies, researchers have made little progress in the field of adoptive cellular therapies for relapsed/refractory acute myeloid leukemia (AML), unlike the notable uptake for B cell malignancies. Various single antigen-targeting chimeric antigen receptor (CAR) T cell Phase I trial...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/15/10/2713 |
| _version_ | 1797600710263570432 |
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| author | Erden Atilla Karim Benabdellah |
| author_facet | Erden Atilla Karim Benabdellah |
| author_sort | Erden Atilla |
| collection | DOAJ |
| description | Despite exhaustive studies, researchers have made little progress in the field of adoptive cellular therapies for relapsed/refractory acute myeloid leukemia (AML), unlike the notable uptake for B cell malignancies. Various single antigen-targeting chimeric antigen receptor (CAR) T cell Phase I trials have been established worldwide and have recruited approximately 100 patients. The high heterogeneity at the genetic and molecular levels within and between AML patients resembles a black hole: a great gravitational field that sucks in everything. One must consider the fact that only around 30% of patients show a response; there are, however, consequential off-tumor effects. It is obvious that a new point of view is needed to achieve more promising results. This review first introduces the unique therapeutic challenges of not only CAR T cells but also other adoptive cellular therapies in AML. Next, recent single-cell sequencing data for AML to assess somatically acquired alterations at the DNA, epigenetic, RNA, and protein levels are discussed to give a perspective on cellular heterogeneity, intercellular hierarchies, and the cellular ecosystem. Finally, promising novel strategies are summarized, including more sophisticated next-generation CAR T, TCR-T, and CAR NK therapies; the approaches with which to tailor the microenvironment and target neoantigens; and allogeneic approaches. |
| first_indexed | 2024-03-11T03:52:43Z |
| format | Article |
| id | doaj.art-6c3b21688cc64fd7af529ffaa0174c46 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T03:52:43Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-6c3b21688cc64fd7af529ffaa0174c462023-11-18T00:47:52ZengMDPI AGCancers2072-66942023-05-011510271310.3390/cancers15102713The Black Hole: CAR T Cell Therapy in AMLErden Atilla0Karim Benabdellah1Fred Hutchinson Cancer Research Center, Clinical Research Division, 1100 Fairview Ave N, Seattle, WA 98109, USAGENYO Centre for Genomics and Oncological Research, Genomic Medicine Department, Pfizer/University of Granada/Andalusian Regional Government, Health Sciences Technology Park, 18016 Granada, SpainDespite exhaustive studies, researchers have made little progress in the field of adoptive cellular therapies for relapsed/refractory acute myeloid leukemia (AML), unlike the notable uptake for B cell malignancies. Various single antigen-targeting chimeric antigen receptor (CAR) T cell Phase I trials have been established worldwide and have recruited approximately 100 patients. The high heterogeneity at the genetic and molecular levels within and between AML patients resembles a black hole: a great gravitational field that sucks in everything. One must consider the fact that only around 30% of patients show a response; there are, however, consequential off-tumor effects. It is obvious that a new point of view is needed to achieve more promising results. This review first introduces the unique therapeutic challenges of not only CAR T cells but also other adoptive cellular therapies in AML. Next, recent single-cell sequencing data for AML to assess somatically acquired alterations at the DNA, epigenetic, RNA, and protein levels are discussed to give a perspective on cellular heterogeneity, intercellular hierarchies, and the cellular ecosystem. Finally, promising novel strategies are summarized, including more sophisticated next-generation CAR T, TCR-T, and CAR NK therapies; the approaches with which to tailor the microenvironment and target neoantigens; and allogeneic approaches.https://www.mdpi.com/2072-6694/15/10/2713acute myeloid leukemiacellular therapieschimeric antigen T cellsT cell receptor T cellsCAR NK cellsRNAseq |
| spellingShingle | Erden Atilla Karim Benabdellah The Black Hole: CAR T Cell Therapy in AML Cancers acute myeloid leukemia cellular therapies chimeric antigen T cells T cell receptor T cells CAR NK cells RNAseq |
| title | The Black Hole: CAR T Cell Therapy in AML |
| title_full | The Black Hole: CAR T Cell Therapy in AML |
| title_fullStr | The Black Hole: CAR T Cell Therapy in AML |
| title_full_unstemmed | The Black Hole: CAR T Cell Therapy in AML |
| title_short | The Black Hole: CAR T Cell Therapy in AML |
| title_sort | black hole car t cell therapy in aml |
| topic | acute myeloid leukemia cellular therapies chimeric antigen T cells T cell receptor T cells CAR NK cells RNAseq |
| url | https://www.mdpi.com/2072-6694/15/10/2713 |
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