Borkner, Lisa and Kaiser, Andrew and van de Kasteele, Willeke and Andreesen, Reinhard and Mackensen, Andreas and Haanen, John B. and Schumacher, Ton N. and Blank, Christian (2010) RNA interference targeting programmed death receptor-1 improves immune functions of tumor-specific T cells. CANCER IMMUNOLOGY IMMUNOTHERAPY, 59 (8). pp. 1173-1183. ISSN 0340-7004,
Full text not available from this repository. (Request a copy)Abstract
Adoptive cell transfer (ACT), either using rapidly expanded tumor infiltrating lymphocytes or T-cell receptor transduced peripheral blood lymphocytes, can be considered one of the most promising approaches in cancer immunotherapy. ACT results in the repopulation of the host with high frequencies of tumor-specific T cells; however, optimal function of these cells within the tumor micro-environment is required to reach long-term tumor clearance. We and others have shown that ongoing anti-tumor immune responses can be impaired by the expression of ligands, such as PD-L1 (B7-H1) on tumor cells. Such inhibitory molecules can affect T cells at the effector phase via their receptor PD-1. PD-L1/PD-1 interaction has indeed been shown crucial in inducing T-cell anergy and maintaining peripheral tolerance. In order to maximize anti-tumor responses, antibodies that target the PD-1/PD-L1 axis are currently in phase I/II trials. Alternatively, a more refined approach could be the selective targeting of PD-1 in tumor-specific T cells to obtain long-term resistance against PD-1-mediated inhibition. We addressed whether this goal could be achieved by means of retroviral siRNA delivery. Effective siRNA sequences resulting in the reduction of surface PD-1 expression led to improved murine as well as human T-cell immune functions in response to PD-L1 expressing melanoma cells. These data suggest that blockade of PD-1-mediated T-cell inhibition through siRNA forms a promising approach to achieve long-lasting enhancement of tumor-specific T-cell function in adoptive T-cell therapy protocols.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | METASTATIC MELANOMA; LYMPHOCYTES-T; IN-VITRO; PHASE-I; THERAPY; PD-1; EXPRESSION; SYSTEM; IMMUNOTHERAPY; TOLERANCE; siRNA; T cell; PD-1; PD-L1; B7-H1 |
| 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: | 20 Jul 2020 07:08 |
| Last Modified: | 20 Jul 2020 07:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24354 |
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