Bispecific killer cell engager-secreting CAR-T cells redirect natural killer specificity to enhance antitumour responses Journal Article


Authors: Fan, Y.; Duan, Y.; Chen, J.; Wang, Y.; Shang, K.; Jiang, J.; Su, L.; Zhou, C.; Sadelain, M.; Huang, H.; Sun, J.
Article Title: Bispecific killer cell engager-secreting CAR-T cells redirect natural killer specificity to enhance antitumour responses
Abstract: T cells and natural killer (NK) cells collaborate to maintain immune homeostasis. Current cancer immunotherapies predominantly rely on the individual application of these cells. Here we use bicistronic vectors to co-express chimeric antigen receptors (CARs) and secreted immune cell engagers (ICEs), leveraging the combined therapeutic potential of both effector cell types. After in vitro validation of immune cell engager secretion and function, various combinatorial approaches are systematically compared in mouse models, identifying a highly effective combination of bispecific killer cell engager (BiKE)-secreting CAR-T cells and NK cells. Beyond a simple combination of conventional CAR-T cells and NK cells, this strategy demonstrates superior efficacy in CD19+ B cell leukaemia and lymphoma and EGFR+ solid tumour models while reducing the dosage dependence on CAR-T cells. Moreover, CAR-T cells and BiKEs targeting distinct antigens exhibit suppression of tumour cells with heterogeneous antigen expression. These findings indicate that combining BiKE-secreting CAR-T cells and NK cells offers a promising strategy to combat tumour antigen heterogeneity and immune evasion. © The Author(s), under exclusive licence to Springer Nature Limited 2025.
Keywords: cell death; cancer immunotherapy; physiology; antigens; tumors; mammals; anti-tumors; therapeutic potentials; t-cells; antigen receptors; natural killer cells; natural killer; immune cells; homoeostasis; bicistronic vector; 'current; bicycles
Journal Title: Nature Biomedical Engineering
ISSN: 2157-846X
Publisher: Nature Publishing Group  
Publication status: Online ahead of print
Date Published: 2025-07-14
Online Publication Date: 2025-07-14
Language: English
DOI: 10.1038/s41551-025-01450-4
PROVIDER: scopus
PUBMED: 40659834
DOI/URL:
Notes: Source: Scopus
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
  1. Michel W J Sadelain
    587 Sadelain