1. Orchestrating NK and T cells via tri-specific nano-antibodies for synergistic antitumor immunity.
- Author
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Ye QN, Zhu L, Liang J, Zhao DK, Tian TY, Fan YN, Ye SY, Liu H, Huang XY, Cao ZT, Shen S, and Wang J
- Subjects
- Animals, Humans, Mice, Cell Line, Tumor, Immunotherapy methods, Neoplasms immunology, Neoplasms therapy, B7-H1 Antigen immunology, NK Cell Lectin-Like Receptor Subfamily C immunology, Female, Tumor Necrosis Factor Receptor Superfamily, Member 9 immunology, Mice, Inbred NOD, Killer Cells, Natural immunology, Nanoparticles chemistry, Antibodies, Monoclonal immunology, CD8-Positive T-Lymphocytes immunology
- Abstract
The functions of natural killer (NK) and T cells in innate and adaptive immunity, as well as their functions in tumor eradication, are complementary and intertwined. Here we show that utilization of multi-specific antibodies or nano-antibodies capable of simultaneously targeting both NK and T cells could be a valuable approach in cancer immunotherapy. Here, we introduce a tri-specific Nano-Antibody (Tri-NAb), generated by immobilizing three types of monoclonal antibodies (mAbs), using an optimized albumin/polyester composite nanoparticle conjugated with anti-Fc antibody. This Tri-NAb, targeting PDL1, 4-1BB, and NKG2A (or TIGIT) simultaneously, effectively binds to NK and CD8
+ T cells, triggering their activation and proliferation, while facilitating their interaction with tumor cells, thereby inducing efficient tumor killing. Importantly, the antitumor efficacy of Tri-NAb is validated in multiple models, including patient-derived tumor organoids and humanized mice, highlighting the translational potential of NK and T cell co-targeting., (© 2024. The Author(s).)- Published
- 2024
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