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

Abstract

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.

• Authors: Yuefeng Hu, Dong Liu, Peilin Cui, Wen Zhang, Hao Chen, Chunmei Piao, Yongcheng Lu, Xuesong Liu, Yue Wang, Jingwei Liu, Xu Lu
• Journal: Investigational new drugs (Invest New Drugs) Vol. 39 Issue 6 Pg. 1538-1548 (12 2021) ISSN: 1573-0646 [Electronic] United States
• PMID: 34387808 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Chemical References

• Interleukin-15
• Oxaliplatin

Topics

• Adult
• Aged
• Animals
• Antineoplastic Combined Chemotherapy Protocols
• Chemotherapy, Adjuvant
• Female
• Humans
• Immunotherapy, Adoptive (methods)
• Interleukin-15 (administration & dosage, pharmacology)
• Lymphocytes (drug effects)
• Male
• Mice
• Middle Aged
• Neoplasm Staging
• Oxaliplatin (administration & dosage, pharmacology)
• Stomach Neoplasms (drug therapy)
• Survival Analysis
• Xenograft Model Antitumor Assays