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IL-15-induced lymphocytes as adjuvant cellular immunotherapy for gastric cancer

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Summary

Objectives To test the antitumor potential of lymphocytes transferred via adoptive cell therapy (ACT) in a mouse model of human gastric cancer (GC), and to evaluate the clinical efficacy and safety of combining lymphocytes as adjuvant therapy with first-line chemotherapy in patients with GC. Methods We constructed a human GC xenograft model in sublethally irradiated 6–8-week-old male NCG mice. MKN-45 cells (1 × 106 cells/mouse) were subcutaneously injected into mice’s flanks. After tumors had become palpable, we randomized the mice into control, ACTIL−2, and ACTIL−15 groups. Human lymphocytes were then injected into mouse tail veins. In addition, 63 human patients with histologically or cytologically confirmed stage III–IV GC randomly received S-1 + oxaliplatin + ACTIL−15 (combination therapy group) or S-1 + oxaliplatin (chemotherapy group). Results In the mouse study, treatment with ACTIL−15 cells inhibited tumor growth on adoptive transfer, and mice that received ACTIL−15 cells had significantly longer survival rates (p < 0.05, ACTIL−15 vs. ACTIL−2). In the human study, the median survival rate of patients in the combination therapy group was 472 days (95% confidence interval [CI], 276–668 days), whereas that of patients in the chemotherapy group was 266 days (95% CI, 200–332 days; p < 0.05). Eleven percent (7/63) of patients had adverse reactions, but these reactions did not interfere with treatment. Conclusion Adoptive transfer of ACTIL−15 cells in a mouse model of GC and in patients with advanced GC treated with S1 + oxaliplatin improved survival rates in both, with an acceptable safety profile.

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Funding

This work was supported by the National Natural Science Foundation of China (No. 81770468), the Beijing Municipal Natural Science Foundation (No. 7162030), and the Beijing Science and Technology Plan Special Issue (No. Z14010101101).

Author information

Author notes

  1. Yuefeng Hu, Dong Liu and Peilin Cui these authors have contributed equally to this study

Authors and Affiliations

  1. Department of Interventional Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China

    Yuefeng Hu

  2. Department of Radiology, The First Hospital of Tsinghua University, Beijing, China

    Dong Liu

  3. Department of Internal Medicine, Beijing Tiantan Hospital, Capital Medical University, Bejing, China

    Peilin Cui

  4. Department of Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Wen Zhang

  5. Department of Surgical Oncology, Lanzhou University Second Hospital, Lanzhou, China

    Hao Chen

  6. Department of Oncology, Institute of Heart Lung and Blood Vessel Diseases, Beijing Anzhen Hospital Affiliated to the Capital Medical University, Beijing, China

    Chunmei Piao

  7. Department of Physiology, Michigan State University, East Lansing, MI, USA

    Yongcheng Lu

  8. Department of Oncology, Beijing Biohealthcare Biotechnology Co, Ltd, Beijing, China

    Xuesong Liu, Yue Wang, Jingwei Liu & Xu Lu

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  1. Yuefeng Hu
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Contributions

Yuefeng Hu and Jingwei Liu: conceptualization, design, and writing (original-draft preparation). Dong Liu, Peilin Cui, and Xu Lu: data curation, writing (reviewing), and editing. Wen Zhang, Hao Chen, and Yongcheng Lu: resources, methodology, and validation. Chunmei Piao: funding acquisition. Xuesong Liu and Yue Wang: validation.

Corresponding author

Correspondence to Jingwei Liu.

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The study was approved by the Ethical Review Board of the Medical Ethics Committee of the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, and PUMC.

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Hu, Y., Liu, D., Cui, P. et al. IL-15-induced lymphocytes as adjuvant cellular immunotherapy for gastric cancer. Invest New Drugs 39, 1538–1548 (2021). https://doi.org/10.1007/s10637-021-01160-z

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