The novel anti-cMet antibody seeMet 12 potentiates sorafenib therapy and radiotherapy in a colorectal cancer model
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F20%3A00078462" target="_blank" >RIV/00209805:_____/20:00078462 - isvavai.cz</a>
Výsledek na webu
<a href="https://www.frontiersin.org/articles/10.3389/fonc.2020.01717/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fonc.2020.01717/full</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3389/fonc.2020.01717" target="_blank" >10.3389/fonc.2020.01717</a>
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
The novel anti-cMet antibody seeMet 12 potentiates sorafenib therapy and radiotherapy in a colorectal cancer model
Popis výsledku v původním jazyce
Rational: cMet is abnormally regulated in gastrointestinal cancer, and is associated with increased invasiveness of the disease and poor overall survival. There are indications that targeted therapy against cMet, alone or in combination with additional cancer therapies, can help improve treatment outcome. Thus, in the present study we investigated the therapeutic efficacy of a novel cMet-targeting antibody therapy in gastrointestinal cancer models, and assessed potential augmenting effects in combination with tyrosine kinase inhibitor (TKI) targeted therapy or radiotherapy. Methods: Three different cMet-targeting antibodies were first characterized with respect to antigen binding and effects on cell viability in vitro. The best performing candidate seeMet 12 was then further assessed for effects on colorectal cancer cell growth, proliferation and migration. Combinations with the TKI-inhibitor sorafenib or external beam radiotherapy were then evaluated for potential additive or synergistic effects in vitro using monolayer- and multicellular tumor spheroid assays. Finally, the combination of seeMet 12 and radiotherapy was evaluated in vivo in a proof-of-concept colorectal cancer xenograft study. Results: Dose-dependent therapeutic effects were demonstrated for all three cMet-targeting antibodies. Monotherapy using seeMet 12 resulted in impaired cellular migration/proliferation and reduced tumor spheroid growth. Moreover, seeMet 12 was able to potentiate therapeutic effects in vitro for both sorafenib and radiotherapy treatments. Finally, the in vivo therapy study demonstrated promising results, where a combination of seeMet 12 and fractionated radiotherapy increased median survival by 79% compared to radiotherapy alone, and tripled maximum survival. Conclusion: The novel anti-cMet antibody seeMet 12 demonstrated therapeutic effects in cMet positive gastrointestinal cancer cells in vitro. Moreover, the addition of seeMet 12 augmented the effects of sorafenib and radiotherapy. An in vivo proof-of-concept study of seeMet 12 and radiotherapy further validated the results. Thus, cMet-targeted therapy should be further explored as a promising approach to increase therapeutic effects, circumvent treatment resistance, and reduce side effects.
Název v anglickém jazyce
The novel anti-cMet antibody seeMet 12 potentiates sorafenib therapy and radiotherapy in a colorectal cancer model
Popis výsledku anglicky
Rational: cMet is abnormally regulated in gastrointestinal cancer, and is associated with increased invasiveness of the disease and poor overall survival. There are indications that targeted therapy against cMet, alone or in combination with additional cancer therapies, can help improve treatment outcome. Thus, in the present study we investigated the therapeutic efficacy of a novel cMet-targeting antibody therapy in gastrointestinal cancer models, and assessed potential augmenting effects in combination with tyrosine kinase inhibitor (TKI) targeted therapy or radiotherapy. Methods: Three different cMet-targeting antibodies were first characterized with respect to antigen binding and effects on cell viability in vitro. The best performing candidate seeMet 12 was then further assessed for effects on colorectal cancer cell growth, proliferation and migration. Combinations with the TKI-inhibitor sorafenib or external beam radiotherapy were then evaluated for potential additive or synergistic effects in vitro using monolayer- and multicellular tumor spheroid assays. Finally, the combination of seeMet 12 and radiotherapy was evaluated in vivo in a proof-of-concept colorectal cancer xenograft study. Results: Dose-dependent therapeutic effects were demonstrated for all three cMet-targeting antibodies. Monotherapy using seeMet 12 resulted in impaired cellular migration/proliferation and reduced tumor spheroid growth. Moreover, seeMet 12 was able to potentiate therapeutic effects in vitro for both sorafenib and radiotherapy treatments. Finally, the in vivo therapy study demonstrated promising results, where a combination of seeMet 12 and fractionated radiotherapy increased median survival by 79% compared to radiotherapy alone, and tripled maximum survival. Conclusion: The novel anti-cMet antibody seeMet 12 demonstrated therapeutic effects in cMet positive gastrointestinal cancer cells in vitro. Moreover, the addition of seeMet 12 augmented the effects of sorafenib and radiotherapy. An in vivo proof-of-concept study of seeMet 12 and radiotherapy further validated the results. Thus, cMet-targeted therapy should be further explored as a promising approach to increase therapeutic effects, circumvent treatment resistance, and reduce side effects.
Klasifikace
Druh
J<sub>imp</sub> - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
30204 - Oncology
Návaznosti výsledku
Projekt
<a href="/cs/project/EF16_019%2F0000868" target="_blank" >EF16_019/0000868: Molekulární, buněčný a klinický přístup ke zdravému stárnutí</a><br>
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2020
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Frontiers in oncology
ISSN
2234-943X
e-ISSN
—
Svazek periodika
10
Číslo periodika v rámci svazku
September 2020
Stát vydavatele periodika
CH - Švýcarská konfederace
Počet stran výsledku
14
Strana od-do
1717
Kód UT WoS článku
000575929900001
EID výsledku v databázi Scopus
2-s2.0-85091534689