Combination immunotherapy with IL-2 surface-modified tumor cell vaccine and PD-1 blockade against renal cell carcinoma

Immunotherapy may be an effective way to prevent postoperative recurrence of renal cell carcinoma. Streptavidin-interleukin-2 (SA-IL-2) surface-modified tumor cell vaccine developed through our protein-anchor technology could induce specific anti-tumor T-cell response, but this immunotherapy can not completely eradicate the tumor. These effector T-cells highly expressed program death receptor-1 (PD-1), and the expression of program death ligand-1 (PD-L1) in tumor environment also was up-regulated after the SA-IL-2-modified vaccine therapy. PD-1/PD-L1 interaction promotes tumor immune evasion. Adding PD-1 blockade to SA-IL-2-modified vaccine therapy increased the number of CD4+ , CD8+ and CD8+ IFN-γ+ but not CD4+ Foxp3+ T-cells. PD-1 blockade could rescue the activity of tumor-specific T lymphocytes induced by the SA-IL-2-modified vaccine. The combination therapy delayed tumor growth and protected mice against a second Renca cells but not melanoma cells challenge. Taken together, PD-1 blockade could reverse the immune evasion in the treatment with SA-IL-2-modified vaccine, and eventually induce a stronger specific anti-tumor immune response against renal cell carcinoma. This article is protected by copyright. All rights reserved.

Cancer science. 2018 Oct 21 [Epub ahead of print]

Xinji Zhang, Xiaojun Shi, Jinlong Li, Zhiming Hu, Jimin Gao, Shihao Wu, Zhaolin Long

Department of Urology, Shunde Hospital, Southern Medical University, Guangdong, 528300, China., Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China., Institute of Biotherapy, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China., Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical University, Wenzhou, 325035, China.