Orchestrating NK and T cells via tri-specific nano-antibodies for synergistic antitumor immunity

Qian-Ni Ye, Long Zhu, Jie Liang, Dong-Kun Zhao, Tai-Yu Tian, Ya-Nan Fan, Si-Yi Ye, Hua Liu, Xiao-Yi Huang, Zhi-Ting Cao, Song Shen () and Jun Wang ()
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Qian-Ni Ye: Guangzhou International Campus
Long Zhu: Guangzhou International Campus
Jie Liang: Guangzhou International Campus
Dong-Kun Zhao: Guangzhou International Campus
Tai-Yu Tian: Guangzhou International Campus
Ya-Nan Fan: Guangzhou International Campus
Si-Yi Ye: Guangzhou International Campus
Hua Liu: Guangzhou International Campus
Xiao-Yi Huang: Guangzhou International Campus
Zhi-Ting Cao: China Pharmaceutical University
Song Shen: Guangzhou International Campus
Jun Wang: Guangzhou International Campus

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-50474-y

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