Novel BCMA-OR-CD38 tandem-dual chimeric antigen receptor T cells robustly control multiple myeloma. 2021

Yaru Feng, and Xiuying Liu, and Xiaorui Li, and Yating Zhou, and Zhiru Song, and Jing Zhang, and Bingjie Shi, and Jianxun Wang
School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China.

BCMA-targeting chimeric antigen receptor (CAR)-T cell therapy has shown remarkable clinical efficacy against multiple myeloma, yet antigen escape and tumor relapse still occur after the use of these therapies. Designing CAR-T therapies that targets multiple antigens simultaneously seems a feasible way to avoid antigen escape, and it has been extensively studied elsewhere. Here, we report novel BCMA-OR-CD38 Tan CAR T cells that can trigger robust cytotoxicity against target cells expressing either BCMA or CD38. We demonstrate that, in in vitro studies, these BCMA-OR-CD38 Tan CAR T cells exhibit similar CAR expression, superior cytotoxicity and antigen-stimulated T cell proliferation as compared to single-targeted CAR T cells or CD38-OR-BCMA Tan CAR T cells. Importantly, these BCMA-OR-CD38 Tan CAR-T cells can achieve complete tumor clearance in myeloma-bearing mice with no relapse observed through the course of these experiments. Finally, this BCMA-OR-CD38 Tan CAR was fully compatible with existing clinical grade T cell manufacturing procedures and can be implemented using current clinical protocols. Taken together, our results present an effective solution to the challenge of antigen escape in BCMA CAR T-cell therapies.

UI MeSH Term Description Entries
D008562 Membrane Glycoproteins Glycoproteins found on the membrane or surface of cells. Cell Surface Glycoproteins,Surface Glycoproteins,Cell Surface Glycoprotein,Membrane Glycoprotein,Surface Glycoprotein,Glycoprotein, Cell Surface,Glycoprotein, Membrane,Glycoprotein, Surface,Glycoproteins, Cell Surface,Glycoproteins, Membrane,Glycoproteins, Surface,Surface Glycoprotein, Cell,Surface Glycoproteins, Cell
D009101 Multiple Myeloma A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY. Myeloma, Plasma-Cell,Kahler Disease,Myeloma, Multiple,Myeloma-Multiple,Myelomatosis,Plasma Cell Myeloma,Cell Myeloma, Plasma,Cell Myelomas, Plasma,Disease, Kahler,Multiple Myelomas,Myeloma Multiple,Myeloma, Plasma Cell,Myeloma-Multiples,Myelomas, Multiple,Myelomas, Plasma Cell,Myelomas, Plasma-Cell,Myelomatoses,Plasma Cell Myelomas,Plasma-Cell Myeloma,Plasma-Cell Myelomas
D009364 Neoplasm Recurrence, Local The local recurrence of a neoplasm following treatment. It arises from microscopic cells of the original neoplasm that have escaped therapeutic intervention and later become clinically visible at the original site. Local Neoplasm Recurrence,Local Neoplasm Recurrences,Locoregional Neoplasm Recurrence,Neoplasm Recurrence, Locoregional,Neoplasm Recurrences, Local,Recurrence, Local Neoplasm,Recurrence, Locoregional Neoplasm,Recurrences, Local Neoplasm,Locoregional Neoplasm Recurrences,Neoplasm Recurrences, Locoregional,Recurrences, Locoregional Neoplasm
D000076962 Receptors, Chimeric Antigen Synthetic cellular receptors that reprogram T-LYMPHOCYTES to selectively bind antigens. Chimeric Antigen Receptor,Chimeric T-Cell Receptor,Artificial T-Cell Receptors,Chimeric Antigen Receptors,Chimeric Immunoreceptors,Chimeric T-Cell Receptors,Antigen Receptor, Chimeric,Antigen Receptors, Chimeric,Artificial T Cell Receptors,Chimeric T Cell Receptor,Chimeric T Cell Receptors,Immunoreceptors, Chimeric,Receptor, Chimeric Antigen,Receptor, Chimeric T-Cell,Receptors, Artificial T-Cell,Receptors, Chimeric T-Cell,T-Cell Receptor, Chimeric,T-Cell Receptors, Artificial,T-Cell Receptors, Chimeric
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013601 T-Lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T Cell,T Lymphocyte,T-Cells,Thymus-Dependent Lymphocytes,Cell, T,Cells, T,Lymphocyte, T,Lymphocyte, Thymus-Dependent,Lymphocytes, T,Lymphocytes, Thymus-Dependent,T Cells,T Lymphocytes,T-Cell,T-Lymphocyte,Thymus Dependent Lymphocytes,Thymus-Dependent Lymphocyte
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D051997 ADP-ribosyl Cyclase 1 A bifunctional enzyme that catalyzes the synthesis and HYDROLYSIS of CYCLIC ADP-RIBOSE (cADPR) from NAD+ to ADP-RIBOSE. It is a cell surface molecule which is predominantly expressed on LYMPHOID CELLS and MYELOID CELLS. Antigens, CD38,CD38 Antigens,ADPR Cyclase CD38,ADPR Cyclase T10,Acute Lymphoblastic Leukemia Cells Antigen CD38,CD38 Antigen,Lymphocyte Differentiation Antigen CD38,NIM-R5 Antigen,T10 Antigen,1, ADP-ribosyl Cyclase,ADP ribosyl Cyclase 1,Antigen, T10,CD38, ADPR Cyclase,Cyclase 1, ADP-ribosyl,Cyclase CD38, ADPR,Cyclase T10, ADPR,NIM R5 Antigen
D053301 B-Cell Maturation Antigen A member of the tumor necrosis factor receptor superfamily found on mature B-LYMPHOCYTES. It has specificity for B CELL ACTIVATING FACTOR and TUMOR NECROSIS FACTOR LIGAND SUPERFAMILY MEMBER 13. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS. Receptors, Tumor Necrosis Factor, Member 17,B Cell Maturation Protein A,BCMA Protein,Tumor Necrosis Factor Receptor Superfamily, Member 17,B Cell Maturation Antigen,Maturation Antigen, B-Cell

Related Publications

Yaru Feng, and Xiuying Liu, and Xiaorui Li, and Yating Zhou, and Zhiru Song, and Jing Zhang, and Bingjie Shi, and Jianxun Wang
January 2020, Biomarker research,
Yaru Feng, and Xiuying Liu, and Xiaorui Li, and Yating Zhou, and Zhiru Song, and Jing Zhang, and Bingjie Shi, and Jianxun Wang
October 2019, Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi,
Yaru Feng, and Xiuying Liu, and Xiaorui Li, and Yating Zhou, and Zhiru Song, and Jing Zhang, and Bingjie Shi, and Jianxun Wang
January 2021, International journal of molecular sciences,
Yaru Feng, and Xiuying Liu, and Xiaorui Li, and Yating Zhou, and Zhiru Song, and Jing Zhang, and Bingjie Shi, and Jianxun Wang
January 2023, Cancer letters,
Yaru Feng, and Xiuying Liu, and Xiaorui Li, and Yating Zhou, and Zhiru Song, and Jing Zhang, and Bingjie Shi, and Jianxun Wang
May 2020, Nature communications,
Yaru Feng, and Xiuying Liu, and Xiaorui Li, and Yating Zhou, and Zhiru Song, and Jing Zhang, and Bingjie Shi, and Jianxun Wang
April 2024, Annals of hematology,
Yaru Feng, and Xiuying Liu, and Xiaorui Li, and Yating Zhou, and Zhiru Song, and Jing Zhang, and Bingjie Shi, and Jianxun Wang
January 2022, PloS one,
Yaru Feng, and Xiuying Liu, and Xiaorui Li, and Yating Zhou, and Zhiru Song, and Jing Zhang, and Bingjie Shi, and Jianxun Wang
October 2018, Molecular pharmaceutics,
Yaru Feng, and Xiuying Liu, and Xiaorui Li, and Yating Zhou, and Zhiru Song, and Jing Zhang, and Bingjie Shi, and Jianxun Wang
January 2021, Frontiers in oncology,
Yaru Feng, and Xiuying Liu, and Xiaorui Li, and Yating Zhou, and Zhiru Song, and Jing Zhang, and Bingjie Shi, and Jianxun Wang
October 2023, Clinical cancer research : an official journal of the American Association for Cancer Research,
Copied contents to your clipboard!