Rudek, Loreen Sophie and Zimmermann, Katharina and Galla, Melanie and Meyer, Johann and Kuehle, Johannes and Stamopoulou, Andriana and Brand, Daniel and Sandalcioglu, I. Erol and Neyazi, Belal and Moritz, Thomas and Rossig, Claudia and Altvater, Bianca and Falk, Christine S. and Abken, Hinrich and Morgan, Michael Alexander and Schambach, Axel (2021) Generation of an NF kappa B-Driven Alpharetroviral "All-in-One" Vector Construct as a Potent Tool for CAR NK Cell Therapy. FRONTIERS IN IMMUNOLOGY, 12: 751138. ISSN 1664-3224,
Full text not available from this repository. (Request a copy)Abstract
Immune cell therapeutics are increasingly applied in oncology. Especially chimeric antigen receptor (CAR) T cells are successfully used to treat several B cell malignancies. Efforts to engineer CAR T cells for improved activity against solid tumors include co-delivery of pro-inflammatory cytokines in addition to CARs, via either constitutive cytokine expression or inducible cytokine expression triggered by CAR recognition of its target antigen-so-called "T cells redirected for universal cytokine-mediated killing" (TRUCKs) or fourth-generation CARs. Here, we tested the hypothesis that TRUCK principles could be expanded to improve anticancer functions of NK cells. A comparison of the functionality of inducible promoters responsive to NFAT or NF kappa B in NK cells showed that, in contrast to T cells, the inclusion of NF kappa B-responsive elements within the inducible promoter construct was essential for CAR-inducible expression of the transgene. We demonstrated that GD2CAR-specific activation induced a tight NF kappa B-promoter-driven cytokine release in NK-92 and primary NK cells together with an enhanced cytotoxic capacity against GD2(+) target cells, also shown by increased secretion of cytolytic cytokines. The data demonstrate biologically relevant differences between T and NK cells that are important when clinically translating the TRUCK concept to NK cells for the treatment of solid malignancies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHIMERIC ANTIGEN RECEPTOR; NATURAL-KILLER-CELLS; T-CELLS; TRANSGENE EXPRESSION; CANCER; ACTIVATION; IMMUNOTHERAPY; HETEROGENEITY; REMISSIONS; LIGAND; immunotherapy; NK cells; chimeric antigen receptor (CAR); tumor microenvironment; immunomodulatory cytokines; alpharetroviral vectors; "all-in-one" TRUCK; NF kappa B |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Sep 2022 09:46 |
| Last Modified: | 14 Sep 2022 09:46 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47455 |
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