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

Result code in 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>

Alternative codes found

RIV/00843989:_____/23:E0110566

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

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

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

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

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

23

Country of publishing house

CH - SWITZERLAND

Number of pages

19

Pages from-to

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UT code for WoS article

001117930500001

EID of the result in the Scopus database

2-s2.0-85179178623