NK92 Expressing Anti-BCMA CAR and Secreted TRAIL for the Treatment of Multiple Myeloma: Preliminary In Vitro Assessment

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61988987%3A17110%2F23%3AA2402NCA" target="_blank" >RIV/61988987:17110/23:A2402NCA - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00843989:_____/23:E0110566

Výsledek na webu

<a href="https://www.webofscience.com/api/gateway?GWVersion=2&SrcAuth=PQPLP&SrcApp=WOS&DestURL=https%3A%2F%2Fwww.proquest.com%2Fdocview%2F2899395535%2Fembedded%2F53CX94WP4EK0D8VP%3Fpq-origsite%3Dwos&DestApp=PQP_ExternalLink&SrcItemId=WOS:001117930500001&SrcAppSID=EUW1ED0E20mZaKU0BzwHjvVf7aULz" target="_blank" >https://www.webofscience.com/api/gateway?GWVersion=2&SrcAuth=PQPLP&SrcApp=WOS&DestURL=https%3A%2F%2Fwww.proquest.com%2Fdocview%2F2899395535%2Fembedded%2F53CX94WP4EK0D8VP%3Fpq-origsite%3Dwos&DestApp=PQP_ExternalLink&SrcItemId=WOS:001117930500001&SrcAppSID=EUW1ED0E20mZaKU0BzwHjvVf7aULz</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3390/cells12232748" target="_blank" >10.3390/cells12232748</a>

Jazyk výsledku

angličtina

Název v původním jazyce

NK92 Expressing Anti-BCMA CAR and Secreted TRAIL for the Treatment of Multiple Myeloma: Preliminary In Vitro Assessment

Popis výsledku v původním jazyce

Multiple myeloma (MM) has witnessed improved patient outcomes through advancements in therapeutic approaches. Notably, allogeneic stem cell transplantation, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies have contributed to enhanced quality of life. Recently, a promising avenue has emerged with chimeric antigen receptor (CAR) T cells targeting B-cell maturation antigen (BCMA), expressed widely on MM cells. To mitigate risks associated with allogenic T cells, we investigated the potential of BCMA CAR expression in natural killer cells (NKs), known for potent cytotoxicity and minimal side effects. Using the NK-92 cell line, we co-expressed BCMA CAR and soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) employing the piggyBac transposon system. Engineered NK cells (CAR-NK-92-TRAIL) demonstrated robust cytotoxicity against a panel of MM cell lines and primary patient samples, outperforming unmodified NK-92 cells with a mean difference in viability of 45.1% (+/- 26.1%, depending on the target cell line). Combination therapy was explored with the proteasome inhibitor bortezomib (BZ) and gamma-secretase inhibitors (GSIs), leading to a significant synergistic effect in combination with CAR-NK-92-TRAIL cells. This synergy was evident in cytotoxicity assays where a notable decrease in MM cell viability was observed in combinatorial therapy compared to single treatment. In summary, our study demonstrates the therapeutic potential of the CAR-NK-92-TRAIL cells for the treatment of MM. The synergistic impact of combining these engineered NK cells with BZ and GSI supports further development of allogeneic CAR-based products for effective MM therapy.

Název v anglickém jazyce

NK92 Expressing Anti-BCMA CAR and Secreted TRAIL for the Treatment of Multiple Myeloma: Preliminary In Vitro Assessment

Popis výsledku anglicky

Multiple myeloma (MM) has witnessed improved patient outcomes through advancements in therapeutic approaches. Notably, allogeneic stem cell transplantation, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies have contributed to enhanced quality of life. Recently, a promising avenue has emerged with chimeric antigen receptor (CAR) T cells targeting B-cell maturation antigen (BCMA), expressed widely on MM cells. To mitigate risks associated with allogenic T cells, we investigated the potential of BCMA CAR expression in natural killer cells (NKs), known for potent cytotoxicity and minimal side effects. Using the NK-92 cell line, we co-expressed BCMA CAR and soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) employing the piggyBac transposon system. Engineered NK cells (CAR-NK-92-TRAIL) demonstrated robust cytotoxicity against a panel of MM cell lines and primary patient samples, outperforming unmodified NK-92 cells with a mean difference in viability of 45.1% (+/- 26.1%, depending on the target cell line). Combination therapy was explored with the proteasome inhibitor bortezomib (BZ) and gamma-secretase inhibitors (GSIs), leading to a significant synergistic effect in combination with CAR-NK-92-TRAIL cells. This synergy was evident in cytotoxicity assays where a notable decrease in MM cell viability was observed in combinatorial therapy compared to single treatment. In summary, our study demonstrates the therapeutic potential of the CAR-NK-92-TRAIL cells for the treatment of MM. The synergistic impact of combining these engineered NK cells with BZ and GSI supports further development of allogeneic CAR-based products for effective MM therapy.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach

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

23

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

19

Strana od-do

—

Kód UT WoS článku

001117930500001

EID výsledku v databázi Scopus

2-s2.0-85179178623