Combined therapy using LHRH‐PE40 and anti‐CD40 dendritic cells substantially eliminate tumor cells. Issue 5 (28th November 2018)

• Record Type: Journal Article
• Authors: Zhang, Limin; Du, TianJiao; Ma, DongBin; Guo, Fang; Li, ZhenWei; Yan, Hua
• Is Part Of: Journal of cellular biochemistry. Volume 120:Issue 5(2019)
• Page Start: 8093
• Page End: 8100
• Publication Date: 2018-11-28
• Subjects: anti‐CD197 cells -- CD40 signaling pathway -- LHRH‐PE40 -- target cells; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.28088
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: LHRH‐PE40 was used to promote the proliferation of bone marrow derived cell (BMDC) and improve the antigen‐presenting ability of BMDC as well as the immune function via the CD40 signal pathway. LHRH‐PE40 was also implicated in cancer treatment, targeting a variety of cancer cells that express luteinizing hormone‐releasing hormone receptor (LHRHR). In the present study, the mechanism and efficacy of LHRH‐PE40 were addressed in the following three aspects. Enzyme‐linked immunosorbent assay was performed to confirm the binding specificity of LHRH‐PE40 to LHRHR. The killing effect of LHRH‐PE40 on target cells was mediated by LHRHR, which specifically killed LHRHR‐positive target cells while the minimal cytotoxicity of LHRHR‐negative cells is negligible. Spiegelmers, a molecule mutually exclusive with GnRH and developed by Sven Klussmann and Dr Sven Klussmann of NOXXON Pharmaceuticals in Germany, demonstrated that LHRH‐PE40 maintains a combinatory characteristics of LHRH and LHRHR. In the end, the mechanism of LHRH‐PE40 underlying induction of apoptosis at low concentration and prolonged conditions was firstly demonstrated by the basic method of detecting apoptosis to induce apoptosis. It provided a scientific basis for clinical application of LHRH‐PE40 and laid a foundation for the further study of LHRH‐PE40 on inducing apoptosis of target cells. The target cells herein refer to tumor cells that overexpress LHRHR. This study shows that activated DC can more effectively promote the proliferation of CD4+ T cells, and initially proved that DC carrying anti‐CD40 antibody promoted the immune treatment of the tumor. Combining LHRH‐PE40 with anti‐CD40 DCs achieved substantially improved efficacy in killing tumor cells.