Preclinical development and evaluation of nanobody-based CD70-specific CAR T cells for the treatment of acute myeloid leukemia

• DOI: 10.1007/s00262-023-03422-6
• Publication Date: 2023-03-17T17:02:43Z
• Authors: Jiali Cheng; Tong Ge; Xiaojian Zhu; Jue Wang; Yuhao Zeng; Wei Mu; Haodong Cai; Zhenyu Dai; Jin Jin; Yongkun Yang; Guang Hu; Xia Mao; Jianfeng Zhou; Li Zhu; Liang Huang
• Keywords: Decitabine; Mass cytometry; Azacitidine

Acute myeloid leukemia (AML) treatment remains challenging. CD70 was reported as a promising AML-specific antigen. Preclinically, CAR T-cell with single-chain-variable fragment (scFv) or truncated CD27 targeting has been to treat AML. However, various disadvantages including spontaneous exhaustion, proteinase-mediated loss of functional receptors, and high immunogenicity, limited its further application clinical settings. Alternatively, the single-variable domain on heavy chain (VHH), also known nanobodies, comparable binding ability specificity, provides an optional solution.We generated knocked-out novel nanobody-based anti-CD70-CAR T-cells (nb70CAR-T) two different VHHs for antigen detection. Next, we detected expression primary AML blasts by flow cytometry associated efficacy nb70CAR-T target density. Finally, epigenetic modulators were investigated regulate cells promote functionality nb70CAR-T.Our exhibited expected tumoricidal against CD70-expressed cell lines blasts. in not consistently potently respond estimated 40.4% patients when level over threshold 1.6 (MFI ratio). Epigenetic modulators, Decitabine Chidamide can up-regulate cells, enhancing nb70CAR-T.CD70 fully supportive role targeted therapy reported. The combinational use could provide new potential