Novel Local “Off-the-Shelf” Immunotherapy for the Treatment of Myeloma Bone Disease

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61988987%3A17110%2F23%3AA2402L2I" target="_blank" >RIV/61988987:17110/23:A2402L2I - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00843989:_____/23:E0110122

Výsledek na webu

<a href="https://www.webofscience.com/wos/woscc/full-record/WOS:000929386100001" target="_blank" >https://www.webofscience.com/wos/woscc/full-record/WOS:000929386100001</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cells12030448" target="_blank" >10.3390/cells12030448</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Novel Local “Off-the-Shelf” Immunotherapy for the Treatment of Myeloma Bone Disease

Popis výsledku v původním jazyce

Myeloma bone disease (MBD) is one of the major complications in multiple myeloma (MM)-the second most frequent hematologic malignancy. It is characterized by the formation of bone lesions due to the local action of proliferating MM cells, and to date, no effective therapy has been developed. In this study, we propose a novel approach for the local treatment of MBD with a combination of natural killer cells (NKs) and mesenchymal stem cells (MSCs) within a fibrin scaffold, altogether known as FINM. The unique biological properties of the NKs and MSCs, joined to the injectable biocompatible fibrin, permitted to obtain an efficient ""off-the-shelf"" ready-to-use composite for the local treatment of MBD. Our in vitro analyses demonstrate that NKs within FINM exert a robust anti-tumor activity against MM cell lines and primary cells, with the capacity to suppress osteoclast activity (similar to 60%) within in vitro 3D model of MBD. Furthermore, NKs' post-thawing cytotoxic activity is significantly enhanced (similar to 75%) in the presence of MSCs, which circumvents the decrease of NKs cytotoxicity after thawing, a well-known issue in the cryopreservation of NKs. To reduce the tumor escape, we combined FINM with other therapeutic agents (bortezomib (BZ), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)), observing a clear therapeutic synergistic effect in vitro. Finally, the therapeutic efficacy of FINM in combination with BZ and TRAIL was assessed in a mouse model of MM, achieving 16-fold smaller tumors compared to the control group without treatment. These results suggest the potential of FINM to serve as an allogeneic ""off-the-shelf"" approach to improve the outcomes of patients suffering from MBD.

Název v anglickém jazyce

Novel Local “Off-the-Shelf” Immunotherapy for the Treatment of Myeloma Bone Disease

Popis výsledku anglicky

Myeloma bone disease (MBD) is one of the major complications in multiple myeloma (MM)-the second most frequent hematologic malignancy. It is characterized by the formation of bone lesions due to the local action of proliferating MM cells, and to date, no effective therapy has been developed. In this study, we propose a novel approach for the local treatment of MBD with a combination of natural killer cells (NKs) and mesenchymal stem cells (MSCs) within a fibrin scaffold, altogether known as FINM. The unique biological properties of the NKs and MSCs, joined to the injectable biocompatible fibrin, permitted to obtain an efficient ""off-the-shelf"" ready-to-use composite for the local treatment of MBD. Our in vitro analyses demonstrate that NKs within FINM exert a robust anti-tumor activity against MM cell lines and primary cells, with the capacity to suppress osteoclast activity (similar to 60%) within in vitro 3D model of MBD. Furthermore, NKs' post-thawing cytotoxic activity is significantly enhanced (similar to 75%) in the presence of MSCs, which circumvents the decrease of NKs cytotoxicity after thawing, a well-known issue in the cryopreservation of NKs. To reduce the tumor escape, we combined FINM with other therapeutic agents (bortezomib (BZ), and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)), observing a clear therapeutic synergistic effect in vitro. Finally, the therapeutic efficacy of FINM in combination with BZ and TRAIL was assessed in a mouse model of MM, achieving 16-fold smaller tumors compared to the control group without treatment. These results suggest the potential of FINM to serve as an allogeneic ""off-the-shelf"" approach to improve the outcomes of patients suffering from MBD.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

<a href="/cs/project/NU21-03-00032" target="_blank" >NU21-03-00032: Nová lokální terapie myelomové kostní nemoci</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

CELLS

ISSN

2073-4409

e-ISSN

—

Svazek periodika

—

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

18

Strana od-do

—

Kód UT WoS článku

000929386100001

EID výsledku v databázi Scopus

2-s2.0-85147812543