title: Local administration of a novel Toll-like receptor 7 agonist in combination with doxorubicin induces durable tumouricidal effects in a murine model of T cell lymphoma.
abstract: BACKGROUND
  Conventional chemotherapy and radiotherapy for the treatment of lymphoma have notable drawbacks, and passive immunotherapy using a monoclonal antibody is restricted to CD20-positive B cell lymphoma. Therefore, new treatment types are urgently required, especially for T cell lymphoma. One type of new antitumour therapy is the use of active immunotherapeutic agents, such as agonists of the Toll-like receptors (TLRs), which facilitate the induction of prolonged antitumour immune responses.
  
  
  METHODS
  We have synthesised a novel TLR7 agonist called SZU-101 and investigated the systemic antitumour effect on a murine model of T cell lymphoma in vivo.
  
  
  RESULTS
  Here, we report that the intratumoural administration of SZU-101 enhanced the effectiveness of a conventionally used chemotherapeutic agent, doxorubicin (DOX). SZU-101 administration improved tumour clearance in a murine model of T cell lymphoma. The novel combination of intratumourally administered SZU-101 and DOX generated strong cytokine production and enhanced the cytotoxic T lymphocyte response, leading to the eradication of both local and distant tumours in tumour-bearing mice.
  
  
  CONCLUSIONS
  These findings suggested that combined active immunotherapy can be developed as a promising treatment for T cell lymphoma, which may further improve the effectiveness of the current standard cyclophosphamide, DOX, vincristine and prednisone (CHOP) therapy.
authors.affiliation: Shenzhen Key Laboratory of Translational Medicine of Tumor, School of Medicine, Shenzhen University, 3688 Nanhai Avenue, Shenzhen, 518060, People's Republic of China. jiangzhu@szu.edu.cn.|Department of Medical Oncology, Sun Yat-Sen University Cancer Center, 651 Dong Feng RD East, Guangzhou, 510060, People's Republic of China. jiangzhu@szu.edu.cn.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Shenzhen Key Laboratory of Translational Medicine of Tumor, School of Medicine, Shenzhen University, 3688 Nanhai Avenue, Shenzhen, 518060, People's Republic of China. ericheshi@163.com.
authors.forename: Shiping
authors.initials: S
authors.lastname: He
authors.affiliation: Shenzhen Key Laboratory of Translational Medicine of Tumor, School of Medicine, Shenzhen University, 3688 Nanhai Avenue, Shenzhen, 518060, People's Republic of China. 295109886@qq.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.affiliation: Shenzhen Key Laboratory of Translational Medicine of Tumor, School of Medicine, Shenzhen University, 3688 Nanhai Avenue, Shenzhen, 518060, People's Republic of China. szuwangzhulin@163.com.|Shenzhen Engineering Lab of Synthetic Biology, School of Medicine, Shenzhen University, 3688 Nanhai Avenue, Shenzhen, 518060, People's Republic of China. szuwangzhulin@163.com.
authors.forename: Zhulin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Shenzhen Engineering Lab of Synthetic Biology, School of Medicine, Shenzhen University, 3688 Nanhai Avenue, Shenzhen, 518060, People's Republic of China. szuliwang@163.com.
authors.forename: Wang
authors.initials: W
authors.lastname: Li
authors.affiliation: Shenzhen Key Laboratory of Translational Medicine of Tumor, School of Medicine, Shenzhen University, 3688 Nanhai Avenue, Shenzhen, 518060, People's Republic of China. szuchenxianxiong@163.com.
authors.forename: Xianxiong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Shenzhen Key Laboratory of Translational Medicine of Tumor, School of Medicine, Shenzhen University, 3688 Nanhai Avenue, Shenzhen, 518060, People's Republic of China. wqjiang@szu.edu.cn.|Department of Medical Oncology, Sun Yat-Sen University Cancer Center, 651 Dong Feng RD East, Guangzhou, 510060, People's Republic of China. wqjiang@szu.edu.cn.
authors.forename: Wenqi
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Shenzhen Key Laboratory of Translational Medicine of Tumor, School of Medicine, Shenzhen University, 3688 Nanhai Avenue, Shenzhen, 518060, People's Republic of China. dzheng@szu.edu.cn.|Shenzhen Engineering Lab of Synthetic Biology, School of Medicine, Shenzhen University, 3688 Nanhai Avenue, Shenzhen, 518060, People's Republic of China. dzheng@szu.edu.cn.
authors.forename: Duo
authors.initials: D
authors.lastname: Zheng
authors.affiliation: Shenzhen Key Laboratory of Translational Medicine of Tumor, School of Medicine, Shenzhen University, 3688 Nanhai Avenue, Shenzhen, 518060, People's Republic of China. gyjin@szu.edu.cn.|Shenzhen Engineering Lab of Synthetic Biology, School of Medicine, Shenzhen University, 3688 Nanhai Avenue, Shenzhen, 518060, People's Republic of China. gyjin@szu.edu.cn.
authors.forename: Guangyi
authors.initials: G
authors.lastname: Jin
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D015153:Blotting, Western; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016399:Lymphoma, T-Cell / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000819:agonists*; D051379:Mice; D008810:Mice, Inbred C57BL; D013386:Succinates / Q000494:pharmacology*; D051199:Toll-Like Receptor 7 / Q000819:agonists*
chemical_list: D000970:Antineoplastic Agents; D008562:Membrane Glycoproteins; C000604281:SZU-101; D013386:Succinates; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D004317:Doxorubicin; D000225:Adenine