# Antitumor Study of Neoantigen-reactive T Cells Co-expressing IL-7 and CCL19 in Mouse Lung Cancer

## TL;DR

Researchers enhanced T cells with IL-7 and CCL19 to improve their ability to fight lung cancer in mice.

## Contribution

The study introduces a novel gene-modified T cell therapy combining IL-7 and CCL19 to enhance anti-tumor efficacy in solid tumors.

## Key findings

- 7×19 NRT cells significantly increased T cell proliferation and tumor infiltration in mouse lung cancer.
- Treatment with 7×19 NRT cells led to tumor suppression and prolonged survival in mice.
- Both 7×19 NRT and conventional NRT treatments were found to be safe.

## Abstract

新抗原反应性T细胞（neoantigen reactive T cell, NRT）具有抑制表达特异性新抗原的肿瘤生长的能力。然而，由于免疫浸润困难和肿瘤微环境的抑制，NRT在实体瘤中的治疗效果有限。本研究针对小鼠肺癌细胞设计出可以同时表达白细胞介素7（interleukin 7, IL-7）和趋化因子19（chemokine C-C motif ligand 19, CCL19）的NRT细胞（7×19 NRT），并对7×19 NRT细胞和常规NRT细胞的抗肿瘤效果差异进行了评估。

针对小鼠Lewis肺癌细胞（Lewis lung carcinoma, LLC）进行了新一代测序和新抗原预测，制备了RNA疫苗，培养了NRT细胞，构建了编码IL-7和CCL19的逆转录病毒载体，转导NRT细胞并成功表达IL-7和CCL19，成功获得了7×19 NRT，并在小鼠体内外对其抗肿瘤效果进行了评估。

7×19 NRT细胞通过分泌IL-7和CCL19显著增强T细胞的增殖和侵袭能力，在小鼠肺癌中实现了显著的抑瘤作用，延长了小鼠的生存期。经7×19 NRT治疗后，T细胞浸润肿瘤组织及肿瘤组织坏死显著增加。此外，7×19 NRT治疗与常规NRT治疗均安全。

通过IL-7和CCL19的表达，NRT细胞的抗实体瘤能力显著增强，这是一种对NRT安全有效的基因修饰。

Overview of identified immunogenic somatic point mutations