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Rational pemetrexed combined with CIK therapy plus anti-PD-1 mAbs administration sequence will effectively promote the efficacy of CIK therapy in non-small cell lung cancer

Cancer Gene Therapy volume 30, pages 277–287 (2023)Cite this article

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Abstract

Cytokine-induced killer (CIK) cells are heterogeneous cells composed mainly of CD3+CD56+ T cells. As an important treatment method of adoptive therapy, it has shown promising efficacy in many clinical trials, especially in combination with multidrug therapy. However, the maximal antitumor efficacy of CIK therapy in the combined administration of multidrug and CIK therapies and which administration scheme can maximize the antitumor efficacy of CIK therapy are still remain unclear. In this study, we observed that pemetrexed administration prior to the injection of CIK cells maximizes the efficacy of CIK therapy. Anti-PD-1 mAbs should be administered prior to CIK cell injection to maximize the efficacy of the therapy. However, administering anti-PD-1 mAbs after CIK cell injection significantly affects the binding rate of anti-PD-1 mAbs to the PD-1 receptor on CIK cells, affecting the efficacy of the antitumor therapy. In conclusion, our study observed that a rational administration sequence of pemetrexed combined with CIK therapy and anti-PD-1 mAbs significantly promotes the efficacy of CIK therapy, providing an experimental basis for the combination therapy mode and regimen of CIK therapy in clinical practice. We hope that this study can provide patients with lung adenocarcinoma with a prolonged survival time.

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Fig. 1: Rational administration sequence of pemetrexed in combination with CIK therapy for non-small cell lung cancer.
Fig. 2: Rational pemetrexed administration sequence will promote CIK cell infiltration.
Fig. 3: Rational administration sequence of pemetrexed combined with CIK therapy plus anti-PD-1 mAbs for non-small cell lung cancer.
Fig. 4: Ratinoal anti-PD-1 administration sequence will promote CIK cell infiltration.
Fig. 5: The initial blood concentration of anti-PD-1 mAbs ultimately determines the occupancy of PD-1 receptors on CIK cells.
Fig. 6: Anti-PD-1 mAbs promote the function of CIK cells via ERK and AKT pathways.
Fig. 7: Schematic illustration of the model of rational drug administration sequence.

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Data availability

The data used and analyzed during this study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank Editage (www.editage.cn) for English language editing.

Funding

This research was supported by grants from the National Natural Science Foundation of China (U20A20375, 81974416, 81872166, 82103001, and 81802873) and the Tianjin Natural Science Foundation (21JCQNJC01430).

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Author notes

  1. These authors contributed equally: Shaochuan Liu, Yuan Meng.

Authors and Affiliations

  1. Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, China

    Shaochuan Liu, Yuan Meng, Liang Liu, Yingge Lv, Feng Wei, Wenwen Yu, Limei Wang, Xiying Zhang, Xiubao Ren & Qian Sun

  2. Key Laboratory of Cancer Prevention and Therapy, Tianjin, China

    Shaochuan Liu, Yuan Meng, Liang Liu, Yingge Lv, Feng Wei, Wenwen Yu, Limei Wang, Xiying Zhang, Xiubao Ren & Qian Sun

  3. Tianjin’s Clinical Research Center for Cancer, Tianjin, China

    Shaochuan Liu, Yuan Meng, Liang Liu, Yingge Lv, Feng Wei, Wenwen Yu, Limei Wang, Xiying Zhang, Xiubao Ren & Qian Sun

  4. Key Laboratory of Cancer Immunology and Biotherapy, Tianjin, China

    Shaochuan Liu, Yuan Meng, Liang Liu, Yingge Lv, Feng Wei, Wenwen Yu, Limei Wang, Xiying Zhang, Xiubao Ren & Qian Sun

  5. Department of Immunology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

    Shaochuan Liu, Yuan Meng, Yingge Lv, Feng Wei, Wenwen Yu, Limei Wang, Xiying Zhang, Xiubao Ren & Qian Sun

  6. Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

    Liang Liu & Xiubao Ren

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  1. Shaochuan Liu
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Contributions

SL contributed to the design of this study, performed most of the experiments, and wrote the manuscript. YM performed in vivo animal experiments. LL and FW contributed to the design and conception of this study. YL contributed to the preparation of some animal specimens. WY performed the flow cytometric detection and analysis. LW and XZ contributed to the culture of CIK cells in vitro. QS and XR supervised the design of the study and revised this manuscript.

Corresponding authors

Correspondence to Xiubao Ren or Qian Sun.

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The authors declare no competing interests.

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Animal experiments were approved by The Animal Ethical and Welfare Committee of Tianjin Medical University Cancer Institute and Hospital.

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Liu, S., Meng, Y., Liu, L. et al. Rational pemetrexed combined with CIK therapy plus anti-PD-1 mAbs administration sequence will effectively promote the efficacy of CIK therapy in non-small cell lung cancer. Cancer Gene Ther 30, 277–287 (2023). https://doi.org/10.1038/s41417-022-00543-5

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  • DOI: https://doi.org/10.1038/s41417-022-00543-5

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