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000304580 1001_ $$aGivi, Sedigheh$$b0
000304580 245__ $$aCRISPR/Cas9 TCR-Edited NKp30 CAR T Cells Exhibit Superior Anti-Tumor Immunity to B7H6-Expressing Leukemia and Melanoma.
000304580 260__ $$aBasel$$bMolecular Diversity Preservation International$$c2025
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000304580 520__ $$aChimeric antigen receptor (CAR) T-cell therapy directed to CD19 and B-cell maturation antigen has revolutionized treatment of B-cell leukemia and lymphoma, and multiple myeloma. However, identifying suitable targets for acute myeloid leukemia (AML) remains challenging due to concurrent expression of potential target antigens on normal hematopoietic stem cells or tissues. As the stress-induced B7H6 molecule is rarely found on normal tissues but expressed on many cancers including AML and melanoma, the NKp30-ligand B7H6 emerges as a promising target for NKp30-based CAR T therapy for these tumors. In this study, we report a comprehensive B7H6 expression analysis on primary AML and melanoma as well as on different tumor cell-lines examined by RT-qPCR and flow cytometry, and efficient anti-tumor reactivity of NKp30-CAR T cells to AML and melanoma. To overcome limitations of autologous CAR T-cell fitness-dependent efficacy and patient-tailored production, we generated CRISPR/Cas9-mediated TCR-knockout (TCRKO) NKp30-CAR T cells as an off-the-shelf approach for CAR T therapy. Functional studies comparing NKp30-CD28 CAR or NKp30-CD137 CAR TCR+ and TCRKO T lymphocytes revealed superior anti-tumoral immunity of NKp30-CD28 CAR TCRKO T cells to AML and melanoma cell lines in vitro, and effective control of tumor burden in an NSG melanoma-xenograft mouse model. In conclusion, these findings highlight the therapeutic potential of NKp30 CAR TCRKO T cells for adoptive T-cell therapy to B7H6-expressing cancers, including melanoma and AML.
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000304580 650_7 $$2Other$$aB7H6 expressing tumors
000304580 650_7 $$2Other$$aCAR T-cell therapy
000304580 650_7 $$2Other$$aNKp30-based CAR T-cell therapy
000304580 650_7 $$2Other$$aacute myeloid leukemia
000304580 650_7 $$2Other$$aimmunotherapy
000304580 650_7 $$2Other$$amelanoma
000304580 7001_ $$00009-0006-3362-6546$$aLohnes, Benedikt J$$b1
000304580 7001_ $$aEbrahimi, Saber$$b2
000304580 7001_ $$aRiedel, Sophie$$b3
000304580 7001_ $$aKhokhali, Sneha$$b4
000304580 7001_ $$aKhan, Shamsul A$$b5
000304580 7001_ $$00009-0001-9092-6290$$aKeller, Maximilian$$b6
000304580 7001_ $$aWölfel, Catherine$$b7
000304580 7001_ $$0P:(DE-He78)d32743f5aa1b7577cded5ce1d6c153bf$$aEchchannaoui, Hakim$$b8
000304580 7001_ $$aBockamp, Ernesto$$b9
000304580 7001_ $$aAndre, Maya C$$b10
000304580 7001_ $$00000-0002-4302-3240$$aAbken, Hinrich$$b11
000304580 7001_ $$00000-0002-4270-2209$$aTheobald, Matthias$$b12
000304580 7001_ $$00000-0002-6714-6923$$aHartwig, Udo F$$b13
000304580 773__ $$0PERI:(DE-600)2019364-6$$a10.3390/ijms26178235$$gVol. 26, no. 17, p. 8235 -$$n17$$p8235$$tInternational journal of molecular sciences$$v26$$x1422-0067$$y2025
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