Safety and Efficacy Evaluation of MSLN-Chimeric Antigen Receptor T Cells Secreting Anti-PD-1 Antibodies in the Treatment of Advanced Metastatic Cancers

Yong Xia1#, Faliang Zhang1,2,3#, Pei Wang5#, Xinhong Guan1#, Xue Wang1 , Shenglan Lai1 , Hui Xue1 , Yanyan Yu1 , Zongchang Song1 *, Jinxing Lou1,2,3* and Qijun Qian1,4,5*

1 Department of Oncology, Shanghai University Affiliated Mengchao Cancer Hospital, China 2 Department of Oncology, Ningbo 5th Hospital (Ningbo Cancer Hospital), China 3 Department of Oncology, Suzhou BenQ Hospital, China 4 Shanghai Cell Therapy Research Institute, China 5 Shanghai Cell Therapy Group, China # These authors contributed equally to this work

^*Correspondance to: Jinxing Lou 

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Abstract:

Objectives: Although Chimeric Antigen Receptor T (CAR-T) cells exhibit a potent therapeutic effect in B-lineage hematologic malignancies, CAR-T therapy for the heterogeneous solid tumors remains challenging. Tumor immunosuppressive micro-environment within the solid tumor may inhibit the activities of the CAR-T cells. To overcome this obstacle, we generated -MSLN-CAR-T cells secreting anti-Programmed cell Death-1 (PD-1) antibodies (αPD-1-MSLN-CAR-T cells) based piggyBac transposon system and performed a pilot study to assess the safety and efficacy of αPD-1- MSLN-CAR-T cells in the treatment of advanced metastatic malignancies. Methods: An exploratory multicenter clinical trial was conducted from July 2018 to July 2019. Advanced patients over-expressed with Mesothelin (MSLN) and Programmed Death-Ligand 1 (PD-L1) received one cycles of αPD-1-MSLN-CAR-T cells with a cell dose of 2 × 106 cells/kg. Nine patients were recruited in this study who met the requirements of the clinical trial. Safety and progression-free survival were the primary endpoints and overall survival was the secondary endpoint. Results: Amongst the 9 cases that participated in the study, 2 cases exhibited a partial remission, and 4 cases achieved stable disease after cell transfusion. The median progression-free survival and overall survival were 4.2 months (95% CI, 2.7–5.7 months) and 6.5 months (95% CI, 4.7–8.3 months), respectively. One case developed fever and Cytokine Release Syndrome (CRS) (grade 1). Most cases had grade 3/4 decreases in lymphocyte counts. Conclusion: Our data primarily indicate that αPD-1-MSLN- CAR-T cell therapy exhibits a demonstrated effect in advanced metastatic malignancies with low toxicities.

Keywords:

Mesothelin; Chimeric antigen receptor; Immunotherapy; PD-1; Malignancy

Cite the Article:

Xia Y, Zhang F, Wang P, Guan X, Wang X, Lai S, et al. Safety and Efficacy Evaluation of MSLN-Chimeric Antigen Receptor T Cells Secreting AntiPD-1 Antibodies in the Treatment of Advanced Metastatic Cancers. World J Surg Surgical Res. 2022;5:1369..