IL-2-free tumor-infiltrating lymphocyte therapy with PD-1 blockade demonstrates potent efficacy in advanced gynecologic cancer

Tumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of...

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Veröffentlicht in:BMC medicine 2024-05, Vol.22 (1), p.207-13, Article 207
Hauptverfasser: Guo, Jing, Wang, Chunyan, Luo, Ning, Wu, Yuliang, Huang, Wei, Zhu, Jihui, Shi, Weihui, Ding, Jinye, Ge, Yao, Liu, Chunhong, Lu, Zhen, Bast, Jr, Robert C, Ai, Guihai, Yang, Weihong, Wang, Rui, Li, Caixia, Chen, Rong, Liu, Shupeng, Jin, Huajun, Zhao, Binghui, Cheng, Zhongping
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Sprache:eng
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Zusammenfassung:Tumor-infiltrating lymphocyte (TIL) therapy has been restricted by intensive lymphodepletion and high-dose intravenous interleukin-2 (IL-2) administration. To address these limitations, we conducted preclinical and clinical studies to evaluate the safety, antitumor activity, and pharmacokinetics of an innovative modified regimen in patients with advanced gynecologic cancer. Patient-derived xenografts (PDX) were established from a local recurrent cervical cancer patient. TILs were expanded ex vivo from minced tumors without feeder cells in the modified TIL therapy regimen. Patients underwent low-dose cyclophosphamide lymphodepletion followed by TIL infusion without intravenous IL-2. The primary endpoint was safety; the secondary endpoints included objective response rate, duration of response, and T cell persistence. In matched patient-derived xenografts (PDX) models, homologous TILs efficiently reduced tumor size (p 
ISSN:1741-7015
1741-7015
DOI:10.1186/s12916-024-03420-0