Harnessing the Power of CAR-NK Cells: A Promising Off-the-Shelf Therapeutic Strategy for CD38-Positive Malignancies

CD38 is highly expressed on multiple myeloma (MM) cells and has been successfully targeted by different target therapy methods. This molecule is a critical prognostic marker in both diffuse large B-cell lymphoma and chronic lymphocytic leukemia. We have designed and generated an anti-CD38 CAR-NK cel...

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Veröffentlicht in:Iranian journal of immunology Jg. 20; H. 4; S. 410 - 426
Hauptverfasser: Asadi, Maryam, Kiani, Razie, Razban, Vahid, Faraji, Seyed Nooreddin, Ahmadi, Amirhossein, Fallahi, Jafar, Ramezani, Amin, Erfani, Nasrollah
Format: Journal Article
Sprache:Englisch
Veröffentlicht: Iran Shiraz Institute for Cancer Research 01.12.2023
Shiraz University of Medical Sciences
Schlagworte:
Annexin V
Antigens
Apoptosis
B-cell lymphoma
car nk cell
cd38
CD38 antigen
Cell Line, Tumor
Chimeric antigen receptors
Chronic lymphocytic leukemia
Cytotoxicity, Immunologic
Flow cytometry
Granzymes - metabolism
Humans
Immunotherapy, Adoptive - methods
Killer Cells, Natural
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphatic leukemia
Lymphocytes B
Malignancy
Multiple myeloma
Natural killer cells
Perforin
Perforin - metabolism
Receptors, Chimeric Antigen - genetics
Receptors, Chimeric Antigen - metabolism
γ-Interferon
CD38
Malignancy
CAR NK Cell
Multiple Myeloma
ISSN:1735-1383, 1735-367X, 1735-367X
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Zusammenfassung:CD38 is highly expressed on multiple myeloma (MM) cells and has been successfully targeted by different target therapy methods. This molecule is a critical prognostic marker in both diffuse large B-cell lymphoma and chronic lymphocytic leukemia. We have designed and generated an anti-CD38 CAR-NK cell applying NK 92 cell line. The approach has potential application as an off-the-shelf strategy for treatment of CD38 positive malignancies. A second generation of anti-CD38 CAR-NK cell was designed and generated, and their efficacy against CD38-positive cell lines was assessed in vitro. The PE-Annexin V and 7-AAD methods were used to determine the percentage of apoptotic target cells. Flow cytometry was used to measure IFN-γ, Perforin, and Granzyme-B production following intracellular staining. Using in silico analyses, the binding capacity and interaction interface were evaluated. Using Lentivirus, cells were transduced with anti-CD38 construct and were expanded. The expression of anti-CD38 CAR on the surface of NK 92 cells was approximately 25%. As we expected from in silico analysis, our designed CD38-chimeric antigen receptor was bound appropriately to the CD38 protein. NK 92 cells that transduced with the CD38 chimeric antigen receptor, generated significantly more IFN-γ, perforin, and granzyme than Mock cells, and successfully lysed Daudi and Jurkat malignant cells in a CD38-dependent manner. The in vitro findings indicated that the anti-CD38 CAR-NK cells have the potential to be used as an off-the-shelf therapeutic strategy against CD38-positive malignancies. It is recommended that the present engineered NK cells undergo additional preclinical investigations before they can be considered for subsequent clinical trial studies.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1735-1383
1735-367X
1735-367X
DOI:10.22034/iji.2023.100424.2691