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Biography
Jiang Li
Prof. Jiang Li
Sun-Yat Sen University, China
Title:  Adoptively transferred tumor-infiltrating lymphocyte immunotherapy following concurrent chemoradiotherapy in patients with advanced cervical cancer: a phase 1 trial
Abstract:
Adoptive cell therapy (ACT) using ex vivo-expanded tumor-infiltrating lymphocytes (TILs) has been reported to induce remarkable clinical response in solid cancers such as melanoma and cervical cancer (CC). Here we conducted a single-arm phase 1 trial (NCT 04443296) of autologous TILs (auto-TILs) following the concurrent chemo-radiotherapy (CCRT) treatment in 27 CC patients with advanced disease stage. TILs from 20 of the 27 patients were successfully expanded, 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. Single-cell transcriptomics revealed that the cytotoxicity, immune checkpoint and activation genes were highly expressed in infused TILs and showed different levels in responders and nonresponders. The HPV-reactive T cells were enriched in infused TILs relative to peripheral blood. Baseline serum cytokine levels and tumor microenvironment immunophenotype maybe impact on clinical response of patients accepted TIL infusion. Totally, this finding supports that treatment of auto-TILs following CCRT was safety in CC, and the baseline immune parameters in peripheral and tumor microenvironments maybe affect the clinical efficacy.