Cbl-b gene silencing in splenic T lymphocytes as a therapeutic strategy to target the prostate cancer RM-1 cell tumors in immune competent mice

Z.-D. Shi, X.-F. Li, L. Hao, Y. Zhao, Y.-X. Wang, B.-Z. Dong, W.-H. Chen, Z.-G. Zhang, Y.-M. Wang, Q. Fu, C.-H. Han, S. Li

Department of Urology, The Affiliated School of Clinical Medicine of Xuzhou Medical College, Xuzhou Central Hospital, Xuzhou, China. bujiniao2008@qq.com

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• Oncology

OBJECTIVE: In recent years, the field of cancer immunotherapy has become a research hotspot and is currently faced with numerous challenges. The objective of this study was to assess the success of cbl-b gene silencing in splenic T lymphocytes as an immune strategy to target the murine prostate cancer RM-1 cells in vitro and solid tumors in vivo.

MATERIALS AND METHODS: For this purpose, cbl-b gene-specific siRNA was designed, synthesized, and was transfected into mouse splenic T lymphocytes, followed by assessment of T cell activation, TH1 cytokine production, and in vitro cytotoxicity against RM-1 cell targets. For in vivo cytotoxicity studies, first the RM-1 tumor model was established in immune competent mice that were later tumor-injected with splenic T lymphocytes transfected with specific shRNA for cbl-b gene silencing.

RESULTS: The data show that the cbl-b gene silencing in T lymphocytes resulted in an enhanced surface expression of CD69 activation marker, elevated production of interleukin (IL)-2 and interferon (IFN)-γ, and their increased cytotoxicity as effectors against RM-1 prostate cancer cells. The tumor injection with cbl-b shRNA-transfected T lymphocytes also resulted in significant reduction of the tumor size as compared with controls.

CONCLUSIONS: cbl-b gene silencing strategy enhanced the immune function of T lymphocytes, increased their cytotoxic potential against RM-1 prostate cancer cells, as well as caused significant suppression of the tumor growth in immune competent mice.

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