Effective cancer immunotherapy based on combination of TLR agonists with stimulation of phagocytosis
| Autor: | Lucie Paďouková, Veronika Caisova, Ondřej Uher, Jindřich Chmelař, Jan Kopecký, Karolina Kvardova, Kamila Masakova, Pavla Nedbalová, Ivana Jochmanova, Gabriela Krejčová, Jan Ženka |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Neutrophils medicine.medical_treatment Phagocytosis Immunology Melanoma Experimental Adenocarcinoma Mannans 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Lymphocytes Tumor-Infiltrating Cancer immunotherapy Cell Line Tumor medicine Immunology and Allergy Animals Pharmacology Toll-like receptor Chemistry Melanoma Toll-Like Receptors Imidazoles Immunotherapy medicine.disease Acquired immune system Tumor Burden Mice Inbred C57BL Pancreatic Neoplasms Teichoic Acids 030104 developmental biology Poly I-C 030220 oncology & carcinogenesis Cancer research Female Lipoteichoic acid Resiquimod |
| Zdroj: | International immunopharmacology. 59 |
| ISSN: | 1878-1705 |
| Popis: | Immunotherapy emerges as a fundamental approach in cancer treatment. Up to date, the efficacy of numerous different immunotherapies has been evaluated. The use of microorganisms or their parts for immune cell activation, referred to as Pathogen-Associated Molecular Patterns (PAMPs), represents highly promising concept. The therapeutic effect of PAMPs can be further amplified by suitable combination of different types of PAMPs such as Toll like receptor (TLR) agonists and phagocytosis activating ligands. Previously, we used the combination of phagocytosis activating ligand (mannan) and mixture of TLR agonists (resiquimod (R-848), poly(I:C), inactivated Listeria monocytogenes) for successful treatment of melanoma in murine B16-F10 model. In the present study, we optimized the composition and timing of previously used mixture. Therapeutic mixture based on well-defined chemical compounds consisted of mannan anchoring to tumor cell surface by biocompatible anchor for membranes (BAM) and TLR agonists resiquimod, poly(I:C), and lipoteichoic acid (LTA). The optimization resulted in (1) eradication of advanced stage progressive melanoma in 83% of mice, (2) acquisition of resistance to tumor re-transplantation, and (3) potential anti-metastatic effect. After further investigation of mechanisms, underlying anti-tumor responses, we concluded that both innate and adaptive immunity are activated and involved in these processes. We tested the efficacy of our treatment in Panc02 murine model of aggressive pancreatic tumor as well. Simultaneous application of agonistic anti-CD40 antibody was necessary to achieve effective therapeutic response (80% recovery) in this model. Our results suggest that herein presented immunotherapeutic approach is a promising cancer treatment strategy with the ability to eradicate not only primary tumors but also metastases. |
| Databáze: | OpenAIRE |
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