Effective cancer immunotherapy based on combination of TLR agonists with stimulation of phagocytosis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12310%2F18%3A43897550" target="_blank" >RIV/60076658:12310/18:43897550 - isvavai.cz</a>
Alternative codes found
RIV/60077344:_____/18:00507384
Result on the web
<a href="https://reader.elsevier.com/reader/sd/pii/S1567576918301413?token=0980ED140562DCE3179EEEA9F46910F0902741B95A7695CFF1482A1EFAF2DD43B32A97973C365B4EF4ECAE47826FA5A3" target="_blank" >https://reader.elsevier.com/reader/sd/pii/S1567576918301413?token=0980ED140562DCE3179EEEA9F46910F0902741B95A7695CFF1482A1EFAF2DD43B32A97973C365B4EF4ECAE47826FA5A3</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.intimp.2018.03.038" target="_blank" >10.1016/j.intimp.2018.03.038</a>
Alternative languages
Result language
angličtina
Original language name
Effective cancer immunotherapy based on combination of TLR agonists with stimulation of phagocytosis
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30204 - Oncology
Result continuities
Project
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Continuities
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2018
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
International Immunopharmacology
ISSN
1567-5769
e-ISSN
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Volume of the periodical
59
Issue of the periodical within the volume
JUN 2018
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
11
Pages from-to
86-96
UT code for WoS article
000434004500011
EID of the result in the Scopus database
2-s2.0-85054442430