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

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• 作者：Jiang Zhu (1) (2)
  Shiping He (1)
  Jie Du (1)
  Zhulin Wang (1) (3)
  Wang Li (3)
  Xianxiong Chen (1)
  Wenqi Jiang (1) (2)
  Duo Zheng (1) (3)
  Guangyi Jin (1) (3)
  
  1. Shenzhen Key Laboratory of Translational Medicine of Tumor ; School of Medicine ; Shenzhen University ; 3688 Nanhai Avenue ; Shenzhen ; 518060 ; People鈥檚 Republic of China
  2. Department of Medical Oncology ; Sun Yat-Sen University Cancer Center ; 651 Dong Feng RD East ; Guangzhou ; 510060 ; People鈥檚 Republic of China
  3. Shenzhen Engineering Lab of Synthetic Biology ; School of Medicine ; Shenzhen University ; 3688 Nanhai Avenue ; Shenzhen ; 518060 ; People鈥檚 Republic of China
  
• 关键词：Toll ; like receptor 7 ; Doxorubicin ; Immunotherapy ; Lymphoma
• 刊名：Journal of Hematology & Oncology
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：8
• 期：1
• 全文大小：1,284 KB
• 参考文献：1. Rezvani, AR, Maloney, DG (2011) Rituximab resistance. Best Pract Res Clin Haematol 24: pp. 203-16 CrossRef
  2. Adams, S (2009) Toll-like receptor agonists in cancer therapy. Immunotherapy 1: pp. 949-64 CrossRef
  3. Boonstra, A, Asselin-Paturel, C, Gilliet, M, Crain, C, Trinchieri, G, Liu, YJ (2003) Flexibility of mouse classical and plasmacytoid-derived dendritic cells in directing T helper type 1 and 2 cell development: dependency on antigen dose and differential toll-like receptor ligation. J Exp Med 197: pp. 101-9 CrossRef
  4. Qi, H, Denning, TL, Soong, L (2003) Differential induction of interleukin-10 and interleukin-12 in dendritic cells by microbial toll-like receptor activators and skewing of T-cell cytokine profiles. Infect Immun 71: pp. 3337-42 3337-3342.2003" target="_blank" title="It opens in new window">CrossRef
  5. Pasare, C, Medzhitov, R (2003) Toll pathway-dependent blockade of CD4鈥?鈥塁D25+ T cell-mediated suppression by dendritic cells. Science 299: pp. 1033-6 31" target="_blank" title="It opens in new window">CrossRef
  6. Zhao, BG, Vasilakos, JP, Tross, D, Smirnov, D, Klinman, DM (2014) Combination therapy targeting toll like receptors 7, 8 and 9 eliminates large established tumors. J Immunotherapy Cancer 2: pp. 12 CrossRef
  7. Lee, J, Chuang, TH, Redecke, V, She, L, Pitha, PM, Carson, DA (2003) Molecular basis for the immunostimulatory activity of guanine nucleoside analogs: activation of Toll-like receptor 7. Proc Natl Acad Sci U S A 100: pp. 6646-51 3/pnas.0631696100" target="_blank" title="It opens in new window">CrossRef
  8. Friedberg, JW, Kelly, JL, Neuberg, D, Peterson, DR, Kutok, JL, Salloum, R (2009) Phase II study of a TLR-9 agonist (1018 ISS) with rituximab in patients with relapsed or refractory follicular lymphoma. Br J Haematol 146: pp. 282-91 365-2141.2009.07773.x" target="_blank" title="It opens in new window">CrossRef
  9. Mason, KA, Neal, R, Hunter, N, Ariga, H, Ang, K, Milas, L (2006) CpG oligodeoxynucleotides are potent enhancers of radio- and chemoresponses of murine tumors. Radiother Oncol 80: pp. 192-8 CrossRef
  10. Dovedi, SJ, Melis, MH, Wilkinson, RW, Adlard, AL, Stratford, IJ, Honeychurch, J (2013) Systemic delivery of a TLR7 agonist in combination with radiation primes durable antitumor immune responses in mouse models of lymphoma. Blood 121: pp. 251-9 32393" target="_blank" title="It opens in new window">CrossRef
  11. Ehrke, MJ, Verstovsek, S, Krawczyk, CM, Ujhazy, P, Zaleskis, G, Maccubbin, DL (1995) Cyclophosphamide plus tumor necrosis factor-alpha chemoimmunotherapy cured mice: life-long immunity and rejection of re-implanted primary lymphoma. Int J Cancer 63: pp. 463-71 30327" target="_blank" title="It opens in new window">CrossRef
  12. Ehrke, MJ, Verstovsek, S, Ujhazy, P, Meer, JM, Eppolito, C, Maccubbin, DL (1998) Doxorubicin plus tumor necrosis factor alpha combination treatments in EL4-lymphoma-bearing C57BL/6 mice. Cancer Immunol Immunother 45: pp. 287-98 CrossRef
  13. Plosker, GL, Figgitt, DP (2003) Rituximab: a review of its use in non-Hodgkin鈥檚 lymphoma and chronic lymphocytic leukaemia. Drugs 63: pp. 803-43 3495-200363080-00005" target="_blank" title="It opens in new window">CrossRef
  14. Mohammad, RM, Wall, NR, Dutcher, JA, Al-Katib, AM (2000) The addition of bryostatin 1 to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy improves response in a CHOP-resistant human diffuse large cell lymphoma xenograft model. Clin Cancer Res 6: pp. 4950-6
  15. Schon, MP, Schon, M (2008) TLR7 and TLR8 as targets in cancer therapy. Oncogene 27: pp. 190-9 38/sj.onc.1210913" target="_blank" title="It opens in new window">CrossRef
  16. Hamm, S, Rath, S, Michel, S, Baumgartner, R (2009) Cancer immunotherapeutic potential of novel small molecule TLR7 and TLR8 agonists. J Immunotoxicol 6: pp. 257-65 3109/15476910903286733" target="_blank" title="It opens in new window">CrossRef
  17. Liu, HY, Hong, YF, Huang, CM, Chen, CY, Huang, TN, Hsueh, YP (2013) TLR7 negatively regulates dendrite outgrowth through the Myd88-c-Fos-IL-6 pathway. J Neurosci 33: pp. 11479-93 3/JNEUROSCI.5566-12.2013" target="_blank" title="It opens in new window">CrossRef
  18. Dudek, AZ, Yunis, C, Harrison, LI, Kumar, S, Hawkinson, R, Cooley, S (2007) First in human phase I trial of 852A, a novel systemic toll-like receptor 7 agonist, to activate innate immune responses in patients with advanced cancer. Clin Cancer Res 13: pp. 7119-25 32.CCR-07-1443" target="_blank" title="It opens in new window">CrossRef
  19. Akhter, A, Masir, N, Elyamany, G, Phang, KC, Mahe, E, Al-Zahrani, AM (2015) Differential expression of Toll-like receptor (TLR) and B cell receptor (BCR) signaling molecules in primary diffuse large B-cell lymphoma of the central nervous system. J Neurooncol 121: pp. 289-96 3" target="_blank" title="It opens in new window">CrossRef
  20. Spaner, DE, Shi, Y, White, D, Mena, J, Hammond, C, Tomic, J (2006) Immunomodulatory effects of Toll-like receptor-7 activation on chronic lymphocytic leukemia cells. Leukemia 20: pp. 286-95 38/sj.leu.2404061" target="_blank" title="It opens in new window">CrossRef
  21. Smith, TJ, Yamamoto, K, Kurata, M, Yukimori, A, Suzuki, S, Umeda, S (2010) Differential expression of Toll-like receptors in follicular lymphoma, diffuse large B-cell lymphoma and peripheral T-cell lymphoma. Exp Mol Pathol 89: pp. 284-90 3" target="_blank" title="It opens in new window">CrossRef
  22. Ignatz-Hoover JJ, Wang H, Moreton SA, Chakrabarti A, Agarwal MK, Sun K et al. The role of TLR8 signaling in acute myeloid leukemia differentiation. Leukemia. 2014. doi:10.1038/leu.2014.293
  23. Lee, SK, Chwee, JY, Ma, CA, Le Bert, N, Huang, CW, Gasser, S (2014) Synergistic anticancer effects of Pam3CSK4 and Ara-C on B-cell lymphoma cells. Clin Cancer Res 20: pp. 3485-95 32.CCR-13-2522" target="_blank" title="It opens in new window">CrossRef
  24. Wu, CC, Hayashi, T, Takabayashi, K, Sabet, M, Smee, DF, Guiney, DD (2007) Immunotherapeutic activity of a conjugate of a Toll-like receptor 7 ligand. Proc Natl Acad Sci U S A 104: pp. 3990-5 3/pnas.0611624104" target="_blank" title="It opens in new window">CrossRef
  25. Broomfield, SA, van der Most, RG, Prosser, AC, Mahendran, S, Tovey, MG, Smyth, MJ (2009) Locally administered TLR7 agonists drive systemic antitumor immune responses that are enhanced by anti-CD40 immunotherapy. J Immunol 182: pp. 5217-24 3826" target="_blank" title="It opens in new window">CrossRef
  26. Zhang, Y, Luo, F, Cai, Y, Liu, N, Wang, L, Xu, D (2011) TLR1/TLR2 agonist induces tumor regression by reciprocal modulation of effector and regulatory T cells. J Immunol 186: pp. 1963-9 320" target="_blank" title="It opens in new window">CrossRef
  27. Carlsson, G, Gullberg, B, Hafstrom, L (1983) Estimation of liver tumor volume using different formulas鈥攁n experimental study in rats. J Cancer Res Clin Oncol 105: pp. 20-3 391826" target="_blank" title="It opens in new window">CrossRef
  
• 刊物主题：Oncology; Hematology; Cancer Research;
• 出版者：BioMed Central
• ISSN：1756-8722

文摘

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.