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Clinical MedicineIn-Press PreviewClinical trialsOncology Open Access | 10.1172/JCI157726

Phase I study of adjuvant immunotherapy with autologous tumor-infiltrating lymphocytes in locally advanced cervical cancer

He Huang,1 Caiping Nie,2 Xiu-feng Liu,2 Bin Song,3 Jian-hui Yue,4 Jingxiao Xu,2 Jia He,2 Kui Li,5 Yan-ling Feng,1 Ting Wan,1 Min Zheng,1 Yanna Zhang,1 Wei-jun Ye,6 Jun-dong Li,1 Yan-fang Li,1 Jun-yun Li,6 Xin-Ping Cao,6 Zhi-min Liu,1 Xiao-Shi Zhang,5 Qing Liu,5 Xi Zhang,7 Ji-Hong Liu,1 and Jiang Li2

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Huang, H. in: JCI | PubMed | Google Scholar |

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Nie, C. in: JCI | PubMed | Google Scholar

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Liu, X. in: JCI | PubMed | Google Scholar

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Song, B. in: JCI | PubMed | Google Scholar

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Yue, J. in: JCI | PubMed | Google Scholar |

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Xu, J. in: JCI | PubMed | Google Scholar

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by He, J. in: JCI | PubMed | Google Scholar

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Li, K. in: JCI | PubMed | Google Scholar

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Feng, Y. in: JCI | PubMed | Google Scholar |

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Wan, T. in: JCI | PubMed | Google Scholar

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Zheng, M. in: JCI | PubMed | Google Scholar

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Zhang, Y. in: JCI | PubMed | Google Scholar

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Ye, W. in: JCI | PubMed | Google Scholar

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Li, J. in: JCI | PubMed | Google Scholar

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Li, Y. in: JCI | PubMed | Google Scholar

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Li, J. in: JCI | PubMed | Google Scholar

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Cao, X. in: JCI | PubMed | Google Scholar |

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Liu, Z. in: JCI | PubMed | Google Scholar

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Zhang, X. in: JCI | PubMed | Google Scholar

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Liu, Q. in: JCI | PubMed | Google Scholar

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Zhang, X. in: JCI | PubMed | Google Scholar

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Liu, J. in: JCI | PubMed | Google Scholar

1Department of Gynecological Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

2Department of Biotherapy, Sun Yat-sen University Cancer Center, Guangzhou, China

3College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China

4Department of Biology, University of Copenhagen, Copenhagen, Denmark

5State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China

6Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China

7BGI-Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Ther, BGI-Shenzhen, Guangzhou, China

Find articles by Li, J. in: JCI | PubMed | Google Scholar |

Published June 21, 2022 - More info

J Clin Invest. https://doi.org/10.1172/JCI157726.
Copyright © 2022, Huang et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published June 21, 2022 - Version history
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Abstract

BACKGROUND. Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) has achieved remarkable clinical efficacy in metastatic cancers such as melanoma and cervical cancer (CC). Here we explored the safety, feasibility and preliminary tumor response and performed translational investigations of adjuvant immunotherapy using infusion of autogenous (auto)-TILs following concurrent chemoradiotherapy (CCRT) in CC patients with locally advanced disease.

METHODS. Twenty-seven CC patients with stage III to IV disease were recruited in this single-center, phase I study. TILs were isolated from lesions in the uterine cervix and generated under good manufacturing practices (GMP) conditions and then infused after CCRT plus intramuscular interleukin (IL)-2 injections.

RESTULTS. From 27 patients, TILs were successfully expanded from 20 patients, with a feasibility of 74.1%. Twelve patients received TILs following CCRT. Adverse events (AEs) were primarily attributable to CCRT. Only 1 (8.3%) patient experienced severe toxicity with a grade 3 hypersensitivity reaction after TIL infusion. No autoimmune AEs, such as pneumonitis, hepatitis, or myocarditis, occurred, and there was no treatment-related mortality. Nine of 12 patients (75.0%) attained complete response, with a disease control duration of 9 to 22 months. Translational investigation showed that the transcriptomic characteristics of the infused TIL products and some immune biomarkers in the tumor microenvironment and serum of CC patients at baseline were correlated with the clinical response.

CONCULSION. TIL-based ACT following CCRT was safe in an academic center setting, with potential effective responses in locally advanced CC patients. ‘Hot’ inflammatory immune environments are beneficial to the clinical efficacy of TIL-based ACT as adjuvant therapy.

TRIAL REGISTRATION. ClinicalTrials.gov NCT04443296.

FUNDING. Natinoal Key R&D Program: Sci-Tech Key Program of the Guangzhou City Science Foundation; the Guangdong Provinve Sci-Tech International Key Program; the National Natural Science Foundation of China.

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