TLR7 agonist in combination with Salmonella as an effective antimelanoma immunotherapy

被引:14
作者
Vola, Magdalena [1 ,2 ]
Monaco, Amy [1 ]
Bascuas, Thais [1 ]
Rimsky, Geraldine [1 ]
Agorio, Caroline Isabel [2 ]
Chabalgoity, Jose Alejandro [1 ]
Moreno, Maria [1 ]
机构
[1] Univ Republica, Fac Med, Inst Higiene, Dept Desarrollo Biotecnol, Av A Navarro 3051, Montevideo 11600, Uruguay
[2] Univ Republica, Fac Med, Hosp Clin Dr Manuel Quintela, Catedra Dermatol, Av Italia S-N, Montevideo, Uruguay
关键词
experimental model; imiquimod; immunotherapy; melanoma; Salmonella; IMIQUIMOD 5-PERCENT CREAM; LIVE ATTENUATED SALMONELLA; CALMETTE-GUERIN BCG; IN-TRANSIT MELANOMA; TOPICAL IMIQUIMOD; METASTATIC MELANOMA; LENTIGO MALIGNA; NEUTROPHIL GRANULOCYTES; SKIN METASTASES; T-CELLS;
D O I
10.2217/imt-2017-0188
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Aim: We evaluated a novel approach combining the use of attenuated Salmonella immunotherapy with a Toll-like receptor agonist, imiquimod, in B16F1 melanoma-bearing mice. Materials & methods: B16F1 melanoma-bearing mice were daily treated with topical imiquimod in combination with one intratumoral injection of attenuated Salmonella enterica serovar Typhimurium LVR01. Results: The combined therapy resulted in retarded tumor growth and prolonged survival. Combination treatment led to an enhancement in the expression of pro-inflammatory cytokines and chemokines in the tumor microenvironment, with a Th1-skewed profile, resulting in a broad antitumor response. The induced immunity was effective in controlling the occurrence of metastasis. Conclusion: Salmonella LVR01 immunotherapy in combination with imiquimod is a novel approach that could be considered as an effective antimelanoma therapy.
引用
收藏
页码:665 / 679
页数:15
相关论文
共 52 条
[1]   Topical TLR7 Agonist Imiquimod Can Induce Immune-Mediated Rejection of Skin Metastases in Patients with Breast Cancer [J].
Adams, Sylvia ;
Kozhaya, Lina ;
Martiniuk, Frank ;
Meng, Tze-Chiang ;
Chiriboga, Luis ;
Liebes, Leonard ;
Hochman, Tsivia ;
Shuman, Nicholas ;
Axelrod, Deborah ;
Speyer, James ;
Novik, Yelena ;
Tiersten, Amy ;
Goldberg, Judith D. ;
Formenti, Silvia C. ;
Bhardwaj, Nina ;
Unutmaz, Derya ;
Demaria, Sandra .
CLINICAL CANCER RESEARCH, 2012, 18 (24) :6748-6757
[2]   Live attenuated Salmonella as a vector for oral cytokine gene therapy in melanoma [J].
Agorio, Caroline ;
Schreiber, Fernanda ;
Sheppard, Mark ;
Mastroeni, Piero ;
Fernandez, Marcelo ;
Martinez, Miguel Angel ;
Chabalgoity, Jose Alejandro .
JOURNAL OF GENE MEDICINE, 2007, 9 (05) :416-423
[3]   Imiquimod: a novel treatment for lentigo maligna [J].
Ahmed, I ;
Berth-Jones, J .
BRITISH JOURNAL OF DERMATOLOGY, 2000, 143 (04) :843-845
[4]   Broad Cross-Presentation of the Hematopoietically Derived PR1 Antigen on Solid Tumors Leads to Susceptibility to PR1-Targeted Immunotherapy [J].
Alatrash, Gheath ;
Mittendorf, Elizabeth A. ;
Sergeeva, Anna ;
Sukhumalchandra, Pariya ;
Qiao, Na ;
Zhang, Mao ;
St. John, Lisa S. ;
Ruisaard, Kathryn ;
Haugen, Christine E. ;
Al-Atrache, Zein ;
Jakher, Haroon ;
Philips, Anne V. ;
Ding, Xiaoling ;
Chen, Jie Qing ;
Wu, Yun ;
Patenia, Rebecca S. ;
Bernatchez, Chantale ;
Vence, Luis M. ;
Radvanyi, Laszlo G. ;
Hwu, Patrick ;
Clise-Dwyer, Karen ;
Ma, Qing ;
Lu, Sijie ;
Molldrem, Jeffrey J. .
JOURNAL OF IMMUNOLOGY, 2012, 189 (11) :5476-5484
[5]   Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4 [J].
Attia, P ;
Phan, GQ ;
Maker, AV ;
Robinson, MR ;
Quezado, MM ;
Yang, JC ;
Sherry, RM ;
Topalian, SL ;
Kammula, US ;
Royal, RE ;
Restifo, NP ;
Haworth, LR ;
Levy, C ;
Mavroukakis, SA ;
Nichol, G ;
Yellin, MJ ;
Rosenberg, SA .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (25) :6043-6053
[6]   Protumor and antitumor functions of neutrophil granulocytes [J].
Brandau, Sven ;
Dumitru, Claudia A. ;
Lang, Stephan .
SEMINARS IN IMMUNOPATHOLOGY, 2013, 35 (02) :163-176
[7]   Tumor-derived chemokine MCP-1/CCL2 is sufficient for mediating tumor tropism of adoptively transferred T cells [J].
Brown, Christine E. ;
Vishwanath, Reena P. ;
Aguilar, Brenda ;
Starr, Renate ;
Najbauer, Joseph ;
Aboody, Karen S. ;
Jensen, Michael C. .
JOURNAL OF IMMUNOLOGY, 2007, 179 (05) :3332-3341
[8]   Ipilimumab-induced colonic perforation [J].
Burdine, Lyle ;
Lai, Keith ;
Laryea, Jonathan A. .
JOURNAL OF SURGICAL CASE REPORTS, 2014, (03)
[9]   Salmonella typhimurium as a basis for a live oral Echinococcus granulosus vaccine [J].
Chabalgoity, JA ;
Moreno, M ;
Carol, H ;
Dougan, G ;
Hormaeche, E .
VACCINE, 2000, 19 (4-5) :460-469
[10]   Expression and immunogenicity of an Echinococcus granulosus fatty acid-binding protein in live attenuated Salmonella vaccine strains [J].
Chabalgoity, JA ;
Harrison, JA ;
Esteves, A ;
deHormaeche, RD ;
Ehrlich, R ;
Khan, CMA ;
Hormaeche, CE .
INFECTION AND IMMUNITY, 1997, 65 (06) :2402-2412