A pilot study of lymphodepletion intensity for peripheral blood mononuclear cell-derived neoantigen-specific CD8 + T cell therapy in patients with advanced solid tumors

Dandan Li, Chao Chen, Jingjing Li, Jianhui Yue, Ya Ding, Hailun Wang, Zhaoduan Liang, Le Zhang, Si Qiu, Geng Liu, Yan Gao, Ying Huang, Dongli Li, Rong Zhang, Wei Liu, Xizhi Wen, Bo Li, Xiaoshi Zhang (), Xi Zhang () and Rui-Hua Xu ()
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Dandan Li: Sun Yat-sen University Cancer Center
Chao Chen: BGI-Shenzhen
Jingjing Li: Sun Yat-sen University Cancer Center
Jianhui Yue: BGI-Shenzhen
Ya Ding: Sun Yat-sen University Cancer Center
Hailun Wang: BGI-Shenzhen
Zhaoduan Liang: BGI-Shenzhen
Le Zhang: BGI-Shenzhen
Si Qiu: BGI-Shenzhen
Geng Liu: BGI-Shenzhen
Yan Gao: BGI-Shenzhen
Ying Huang: BGI-Shenzhen
Dongli Li: BGI-Shenzhen
Rong Zhang: Sun Yat-sen University Cancer Center
Wei Liu: Sun Yat-sen University Cancer Center
Xizhi Wen: Sun Yat-sen University Cancer Center
Bo Li: BGI-Shenzhen
Xiaoshi Zhang: Sun Yat-sen University Cancer Center
Xi Zhang: BGI-Shenzhen
Rui-Hua Xu: State Key Laboratory of Oncology in South China

Nature Communications, 2023, vol. 14, issue 1, 1-11

Abstract: Abstract Currently, the optimal lymphodepletion intensity for peripheral blood mononuclear cell-derived neoantigen-specific CD8 + T cell (Neo-T) therapy has yet to be determined. We report a single-arm, open-label and non-randomized phase 1 study (NCT02959905) of Neo-T therapy with lymphodepletion at various dose intensity in patients with locally advanced or metastatic solid tumors that are refractory to standard therapies. The primary end point is safety and the secondary end points are disease control rate (DCR), progression-free survival (PFS), overall survival (OS). Results show that the treatment is well tolerated with lymphopenia being the most common adverse event in the highest-intensity lymphodepletion groups. Neo-T infusion-related adverse events are only grade 1–2 in the no lymphodepletion group. The median PFS is 7.1 months (95% CI:3.7-9.8), the median OS is 16.8 months (95% CI: 11.9-31.7), and the DCR is 66.7% (6/9) among all groups. Three patients achieve partial response, two of them are in the no lymphodepletion group. In the group without lymphodepletion pretreatment, one patient refractory to prior anti-PD1 therapy shows partial response to Neo-T therapy. Neoantigen specific TCRs are examined in two patients and show delayed expansion after lymphodepletion treatment. In summary, Neo-T therapy without lymphodepletion could be a safe and promising regimen for advanced solid tumors.

Date: 2023
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DOI: 10.1038/s41467-023-39225-7

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