Effective cancer immunotherapy based on combination of TLR agonists with stimulation of phagocytosis

0507384 - BC 2020 RIV NL eng J - Článek v odborném periodiku
Caisová, V. - Uher, O. - Nedbalová, P. - Jochmanová, I. - Kvardová, K. - Masáková, K. - Krejčová, G. - Paďouková, L. - Chmelař, J. - Kopecký, Jan - Ženka, J.
Effective cancer immunotherapy based on combination of TLR agonists with stimulation of phagocytosis.
International Immunopharmacology. Roč. 59, JUN 2018 (2018), s. 86-96. ISSN 1567-5769. E-ISSN 1878-1705
Institucionální podpora: RVO:60077344
Klíčová slova: receptor agonists * dendritic cells * innate immunity * tumor * vaccination * expression * therapy * Melanoma B16-F10 * Panc02 * TLR agonists * Phagocytosis * Cancer immunotherapy * Metastasis
Obor OECD: Immunology
Impakt faktor: 3.361, rok: 2018
Způsob publikování: Omezený přístup
https://www.sciencedirect.com/science/article/pii/S1567576918301413

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.
Trvalý link: http://hdl.handle.net/11104/0298380