Challenges and Advances in Chimeric Antigen Receptor Therapy for Acute Myeloid Leukemia
The advent of chimeric antigen receptor (CAR) T-cell therapy has led to dramatic remission rates in multiple relapsed/refractory hematologic malignancies. While CAR T-cell therapy has been particularly successful as a treatment for B-cell malignancies, effectively treating acute myeloid leukemia (AM...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/14/3/497 |
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| author | Jennifer Marvin-Peek Bipin N. Savani Oluwole O. Olalekan Bhagirathbhai Dholaria |
| author_facet | Jennifer Marvin-Peek Bipin N. Savani Oluwole O. Olalekan Bhagirathbhai Dholaria |
| author_sort | Jennifer Marvin-Peek |
| collection | DOAJ |
| description | The advent of chimeric antigen receptor (CAR) T-cell therapy has led to dramatic remission rates in multiple relapsed/refractory hematologic malignancies. While CAR T-cell therapy has been particularly successful as a treatment for B-cell malignancies, effectively treating acute myeloid leukemia (AML) with CARs has posed a larger challenge. AML not only creates an immunosuppressive tumor microenvironment that dampens CAR T-cell responses, but it also lacks many unique tumor-associated antigens, making leukemic-specific targeting difficult. One advantage of CAR T-cell therapy compared to alternative treatment options is the ability to provide prolonged antigen-specific immune effector and surveillance functions. Since many AML CAR targets under investigation including CD33, CD117, and CD123 are also expressed on hematopoietic stem cells, CAR T-cell therapy can lead to severe and potentially lethal myeloablation. Novel strategies to combat these issues include creation of bispecific CARs, CAR T-cell “safety switches”, TCR-like CARs, NK CARs, and universal CARs, but all vary in their ability to provide a sustained remission, and consolidation with an allogeneic hematopoietic cell transplantation (allo-HCT) will be necessary in most cases This review highlights the delicate balance between effectively eliminating AML blasts and leukemic stem cells, while preserving the ability for bone marrow to regenerate. The impact of CAR therapy on treatment landscape of AML and changing scope of allo-HCT is discussed. Continued advances in AML CAR therapy would be of great benefit to a disease that still has high morbidity and mortality. |
| first_indexed | 2024-03-10T00:08:43Z |
| format | Article |
| id | doaj.art-fc34ec5f37d34927993c88066ad34425 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T00:08:43Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-fc34ec5f37d34927993c88066ad344252023-11-23T16:03:50ZengMDPI AGCancers2072-66942022-01-0114349710.3390/cancers14030497Challenges and Advances in Chimeric Antigen Receptor Therapy for Acute Myeloid LeukemiaJennifer Marvin-Peek0Bipin N. Savani1Oluwole O. Olalekan2Bhagirathbhai Dholaria3Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USADepartment of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USAThe advent of chimeric antigen receptor (CAR) T-cell therapy has led to dramatic remission rates in multiple relapsed/refractory hematologic malignancies. While CAR T-cell therapy has been particularly successful as a treatment for B-cell malignancies, effectively treating acute myeloid leukemia (AML) with CARs has posed a larger challenge. AML not only creates an immunosuppressive tumor microenvironment that dampens CAR T-cell responses, but it also lacks many unique tumor-associated antigens, making leukemic-specific targeting difficult. One advantage of CAR T-cell therapy compared to alternative treatment options is the ability to provide prolonged antigen-specific immune effector and surveillance functions. Since many AML CAR targets under investigation including CD33, CD117, and CD123 are also expressed on hematopoietic stem cells, CAR T-cell therapy can lead to severe and potentially lethal myeloablation. Novel strategies to combat these issues include creation of bispecific CARs, CAR T-cell “safety switches”, TCR-like CARs, NK CARs, and universal CARs, but all vary in their ability to provide a sustained remission, and consolidation with an allogeneic hematopoietic cell transplantation (allo-HCT) will be necessary in most cases This review highlights the delicate balance between effectively eliminating AML blasts and leukemic stem cells, while preserving the ability for bone marrow to regenerate. The impact of CAR therapy on treatment landscape of AML and changing scope of allo-HCT is discussed. Continued advances in AML CAR therapy would be of great benefit to a disease that still has high morbidity and mortality.https://www.mdpi.com/2072-6694/14/3/497immunotherapychimeric antigen receptoracute myeloid leukemiabone marrow transplantation |
| spellingShingle | Jennifer Marvin-Peek Bipin N. Savani Oluwole O. Olalekan Bhagirathbhai Dholaria Challenges and Advances in Chimeric Antigen Receptor Therapy for Acute Myeloid Leukemia Cancers immunotherapy chimeric antigen receptor acute myeloid leukemia bone marrow transplantation |
| title | Challenges and Advances in Chimeric Antigen Receptor Therapy for Acute Myeloid Leukemia |
| title_full | Challenges and Advances in Chimeric Antigen Receptor Therapy for Acute Myeloid Leukemia |
| title_fullStr | Challenges and Advances in Chimeric Antigen Receptor Therapy for Acute Myeloid Leukemia |
| title_full_unstemmed | Challenges and Advances in Chimeric Antigen Receptor Therapy for Acute Myeloid Leukemia |
| title_short | Challenges and Advances in Chimeric Antigen Receptor Therapy for Acute Myeloid Leukemia |
| title_sort | challenges and advances in chimeric antigen receptor therapy for acute myeloid leukemia |
| topic | immunotherapy chimeric antigen receptor acute myeloid leukemia bone marrow transplantation |
| url | https://www.mdpi.com/2072-6694/14/3/497 |
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