Vatter, Sarah and Schmid, Maximilian and Gebhard, Claudia and Mirbeth, Carina and Klobuch, Sebastian and Rehli, Michael and Herr, Wolfgang and Thomas, Simone (2018) In-vitro blockade of the CD4 receptor co-signal in antigen-specific T-cell stimulation cultures induces the outgrowth of potent CD4 independent T-cell effectors. JOURNAL OF IMMUNOLOGICAL METHODS, 454. pp. 80-85. ISSN 0022-1759, 1872-7905
Full text not available from this repository. (Request a copy)Abstract
T-cell receptor (TCR) redirected T cells are promising tools for adoptive cancer immunotherapy. Since not only CD8 but also CD4 T cells are key players for efficient antitumor responses, the targeted redirection of both subsets with the same antigen-specific TCR comes more and more into focus, Although rapidly evolving technologies enable the reliable genetic re-programming of T cells, the limited availability of TCRs that induce T-cell activation in both T-cell subsets without CD4/CD8 co-receptor contribution hampers the broad application of this approach. We developed a novel stimulation approach, which drives the activation and proliferation of CD4 T-cell populations capable of inducing effector functions in a CD4-independent manner. Naive-enriched CD4 T cells were stimulated against dendritic cells (DC) expressing allogeneic HLA-DP antigens upon RNA transfection and CD4/HLA interactions were blocked by the addition of CD4 binding antibody. Evolving CD4 T-cell populations were specifically activated independent of the CD4 co-signal and induced strong TCR-mediated IFN-gamma secretion as well as cytolysis upon recognition of leukemia cells expressing HLA-DP antigen. Our novel stimulation approach may facilitate the generation of CD4 T cells as source for co-receptor independent TCRs for future immunotherapies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | IMMUNOTHERAPY; LEUKEMIA; REJECTION; THERAPY; DISPLAY; MICE; TCR; Immunotherapy; T-cell receptor; CD4 T cells; CD4 co-receptor; Leukemia; HLA-DP |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Mar 2020 12:52 |
| Last Modified: | 16 Mar 2020 12:52 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14980 |
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