The combination of immunotherapy and a glutamine metabolism inhibitor represents an effective therapeutic strategy for advanced and metastatic murine pancreatic adenocarcinoma
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00570994" target="_blank" >RIV/61388963:_____/23:00570994 - isvavai.cz</a>
Alternative codes found
RIV/60076658:12310/23:43906528
Result on the web
<a href="https://doi.org/10.1016/j.intimp.2023.110150" target="_blank" >https://doi.org/10.1016/j.intimp.2023.110150</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.intimp.2023.110150" target="_blank" >10.1016/j.intimp.2023.110150</a>
Alternative languages
Result language
angličtina
Original language name
The combination of immunotherapy and a glutamine metabolism inhibitor represents an effective therapeutic strategy for advanced and metastatic murine pancreatic adenocarcinoma
Original language description
Despite constant advances in cancer research, the treatment of pancreatic adenocarcinoma remains extremely challenging. The intratumoral immunotherapy approach that was developed by our research group and was based on a combination of mannan-BAM, TLR ligands, and anti-CD40 antibody (MBTA) showed promising therapeutic effects in various murine tumor models, including a pancreatic adenocarcinoma model (Panc02). However, the efficacy of MBTA therapy in the Panc02 model was negatively correlated with tumor size at the time of therapy initiation. Here, we aimed to further improve the outcome of MBTA therapy in the Panc02 model using the glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON). The combination of intratumoral MBTA therapy and intraperitoneal administration of DON resulted in the complete elimination of advanced Panc02 subcutaneous tumors (140.8 ± 46.8 mm3) in 50% of treated animals and was followed by development of long-term immune memory. In the bilateral Panc02 subcutaneous tumor model, we observed a significant reduction in tumor growth in both tumors as well as prolonged survival of treated animals. The appropriate timing and method of administration of DON were also addressed to maximize its therapeutic effects and minimize its side effects. In summary, our findings demonstrate that the intraperitoneal application of DON significantly improves the efficacy of intratumoral MBTA therapy in both advanced and bilateral Panc02 subcutaneous tumor murine models.
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
30107 - Medicinal chemistry
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
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
1878-1705
Volume of the periodical
118
Issue of the periodical within the volume
May
Country of publishing house
NL - THE KINGDOM OF THE NETHERLANDS
Number of pages
7
Pages from-to
110150
UT code for WoS article
000982156400001
EID of the result in the Scopus database
2-s2.0-85151515863