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

Author

Listed:
  • Qian-Ni Ye

    (Guangzhou International Campus
    South China University of Technology)

  • 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
    South China University of Technology)

  • 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
    South China University of Technology)

  • Jun Wang

    (Guangzhou International Campus
    South China University of Technology
    South China University of Technology)

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.

Suggested Citation

  • 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 & Jun Wang, 2024. "Orchestrating NK and T cells via tri-specific nano-antibodies for synergistic antitumor immunity," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50474-y
    DOI: 10.1038/s41467-024-50474-y
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    1. Cheng-Tao Jiang & Kai-Ge Chen & An Liu & Hua Huang & Ya-Nan Fan & Dong-Kun Zhao & Qian-Ni Ye & Hou-Bing Zhang & Cong-Fei Xu & Song Shen & Meng-Hua Xiong & Jin-Zhi Du & Xian-Zhu Yang & Jun Wang, 2021. "Immunomodulating nano-adaptors potentiate antibody-based cancer immunotherapy," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    2. Xinyue Qi & Fanlin Li & Yi Wu & Chen Cheng & Ping Han & Jieyi Wang & Xuanming Yang, 2019. "Optimization of 4-1BB antibody for cancer immunotherapy by balancing agonistic strength with FcγR affinity," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    3. Olivier Demaria & Stéphanie Cornen & Marc Daëron & Yannis Morel & Ruslan Medzhitov & Eric Vivier, 2019. "Publisher Correction: Harnessing innate immunity in cancer therapy," Nature, Nature, vol. 576(7785), pages 3-3, December.
    4. Edward Seung & Zhen Xing & Lan Wu & Ercole Rao & Virna Cortez-Retamozo & Beatriz Ospina & Liqing Chen & Christian Beil & Zhili Song & Bailin Zhang & Mikhail Levit & Gejing Deng & Andrew Hebert & Patri, 2022. "A trispecific antibody targeting HER2 and T cells inhibits breast cancer growth via CD4 cells," Nature, Nature, vol. 603(7900), pages 328-334, March.
    5. Olivier Demaria & Stéphanie Cornen & Marc Daëron & Yannis Morel & Ruslan Medzhitov & Eric Vivier, 2019. "Harnessing innate immunity in cancer therapy," Nature, Nature, vol. 574(7776), pages 45-56, October.
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