Lenalidomide enhances antitumor functions of chimeric antigen receptor modified T cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F16%3A00472010" target="_blank" >RIV/68378050:_____/16:00472010 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/16:10325496 RIV/00064165:_____/16:10325496

Result on the web

<a href="http://dx.doi.org/10.1080/2162402X.2015.1115940" target="_blank" >http://dx.doi.org/10.1080/2162402X.2015.1115940</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1080/2162402X.2015.1115940" target="_blank" >10.1080/2162402X.2015.1115940</a>

Result language

angličtina

Original language name

Lenalidomide enhances antitumor functions of chimeric antigen receptor modified T cells

Original language description

Tumor immunotherapy based on the use of chimeric antigen receptor modified T cells (CAR T cells) is a promising approach for the treatment of refractory hematological malignancies. However, a robust response mediated by CAR T cells is observed only in a minority of patients and the expansion and persistence of CAR T cells in vivo is mostly unpredictable.Lenalidomide (LEN) is an immunomodulatory drug currently approved for the treatment of multiple myeloma (MM) and mantle cell lymphoma, while it is clinically tested in the therapy of diffuse large B-cell lymphoma of activated B cell immunophenotype. LEN was shown to increase antitumor immune responses at least partially by modulating the activity of E3 ubiquitin ligase Cereblon, which leads to increased ubiquitinylation of Ikaros and Aiolos transcription factors, which in turn results in changed expression of various receptors on the surface of tumor cells. In order to enhance the effectiveness of CAR-based immunotherapy, we assessed the anti-lymphoma efficacy of LEN in combination with CAR19 T cells or CAR20 T cells in vitro and in vivo using various murine models of aggressive B-cell non-Hodgkin lymphomas (B-NHL).Immunodeficient NSG mice were transplanted with various human B-NHL cells followed by treatment with CAR19 or CAR20 T cells with or without LEN. Next, CAR19 T cells were subjected to series of tests in vitro to evaluate their response and signaling capacity following recognition of B cell in the presence or absence of LEN.Our data shows that LEN significantly enhances antitumor functions of CAR19 and CAR20 T cells in vivo. Additionally, it enhances production of interferon gamma by CAR19 T cells and augments cell signaling via CAR19 protein in T cells in vitro. Our data further suggests that LEN works through direct effects on T cells but not on B-NHL cells. The biochemical events underlying this costimulatory effect of LEN are currently being investigated. In summary, our data supports the use of LEN f...

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

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

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2016

Confidentiality

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

Name of the periodical

ONCOIMMUNOLOGY

ISSN

2162-402X

e-ISSN

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Volume of the periodical

5

Issue of the periodical within the volume

4

Country of publishing house

US - UNITED STATES

Number of pages

10

Pages from-to

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UT code for WoS article

000374194200029

EID of the result in the Scopus database

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