Targeting CD5 chimeric antigen receptor-engineered natural killer cells against T-cell malignancies

• DOI: 10.1186/s40164-024-00577-5
• Publication Date: 2024-10-26T07:01:43Z
• Authors: Yingling Zu; Quan Ren; Jishuai Zhang; Hongchang Su; Qiumei Lu; Yongping Song; Jian Zhou
• Keywords: Genetically engineered

Abstract Background Chimeric antigen receptor engineered T cells (CAR-T) have demonstrated promising clinical efficacy in B-cell malignancies, and the approach has been extended to T-cell malignancies. However, use of allogeneic CAR therapy poses a challenge due risk graft-versus-host disease. Recently, natural killer (NK) exhibited “off‑the‑shelf” availability. The nanobody-based structures attracted much attention for their therapeutic potential owing advantages nanobody, including small size, optimal stability, high affinity manufacturing feasibility. CD5, common surface marker malignant cells, three scavenger cysteine-rich domains (D1-D3) extracellular region. present study aims construct CAR-NK targeting membrane-proximal domain CD5 derived from nanobody against Methods Anti-CD5-D3 was screened by phage display technology, followed constructing fourth-generation plasmids ectopically producing IL-15 generate peripheral blood. And second-generation CAR-T based on were generated, referred as 5D.b 12 C.b CAR-T. Furthermore, without (IL-15 △ CAR-NK) generated assess impact cytotoxicity cells. Cytotoxic activity + hematologic cell lines normal exerted vitro NOD/ShiLtJGpt-Prkdcem26Cd52Il2rgem26Cd22/Gpt mouse model transplanted with Jurkat-Luc used evaluate antitumor vivo. Results Two nanobodies (5D C) competed binding epitope CD5-D3. C superior 5D cytotoxic than ex So, regarded nanobody. robust controlled disease progression xenograft model. greater compared that Conclusions Taken together, nanobody-derived anti-CD5 may be