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宫颈癌免疫微环境的调控及自体肿瘤浸润T淋巴细胞（TIL）联合同时期放化疗辅助治疗I期临床试验研究

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, translational investigations for 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. Of 27 patients, 20 cases were successfully generated expanded TILs with a feasibility of 74.1%. Twelve patients received TILs following CCRT. Adverse events (AEs) were attributable primarily 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, were appeared, neither 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 infused TIL products and some immune biomarkers in tumor microenvironments 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.

248 2022-06-13

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