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

Result code in 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>

Alternative codes found

RIV/00843989:_____/23:E0110122

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10601 - Cell biology

Project

<a href="/en/project/NU21-03-00032" target="_blank" >NU21-03-00032: A novel local therapy for myeloma bone disease</a><br>

Continuities

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

Publication year

2023

Confidentiality

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

Name of the periodical

CELLS

ISSN

2073-4409

e-ISSN

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Volume of the periodical

—

Issue of the periodical within the volume

3

Country of publishing house

CH - SWITZERLAND

Number of pages

18

Pages from-to

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UT code for WoS article

000929386100001

EID of the result in the Scopus database

2-s2.0-85147812543