Multhoff, Gabriele and Seier, Sophie and Stangl, Stefan and Sievert, Wolfgang and Shevtsov, Maxim and Werner, Caroline and Pockley, A. Graham and Blankenstein, Christiane and Hildebrandt, Martin and Offner, Robert and Ahrens, Norbert and Kokowski, Konrad and Hautmann, Matthias and Roedel, Claus and Fietkau, Rainer and Lubgan, Dorota and Huber, Rudolf and Hautmann, Hubert and Duell, Thomas and Molls, Michael and Specht, Hanno and Haller, Bernhard and Devecka, Michal and Sauter, Andreas and Combs, Stephanie E. (2020) Targeted Natural Killer Cell-Based Adoptive Immunotherapy for the Treatment of Patients with NSCLC after Radiochemotherapy: A Randomized Phase II Clinical Trial. CLINICAL CANCER RESEARCH, 26 (20). pp. 5368-5379. ISSN 1078-0432, 1557-3265
Full text not available from this repository. (Request a copy)Abstract
Purpose: Non-small cell lung cancer (NSCLC) is a fatal disease with poor prognosis. Amembrane-bound form of Hsp70 (mHsp70) which is selectively expressed on high-risk tumors serves as a target for mHsp70-targeting natural killer (NK) cells. Patients with advanced mHsp70-positive NSCLC may therefore benefit from a therapeutic intervention involving mHsp70-targeting NK cells. The randomized phase II clinical trial (EudraCT2008-002130-30) explores tolerability and efficacy of ex vivo-activated NK cells in patients with NSCLC after radiochemotherapy (RCT). Patients and Methods: Patients with unresectable, mHsp70-positive NSCLC (stage IIIa/b) received 4 cycles of autologous NK cells activated ex vivo with TKD/IL2 [interventional arm (INT)] after RCT (60-70 Gy, platinum-based chemotherapy) or RCT alone [control arm (CTRL)]. The primary objective was progression-free survival (PFS), and secondary objectives were the assessment of quality of life (QoL, QLQ-LC13), toxicity, and immunobiological responses. Results: The NK-cell therapy after RCT was well tolerated, and no differences in QoL parameters between the two study arms were detected. Estimated 1-year probabilities for PFS were 67% [95% confidence interval (CI), 19%-90%] for the INT arm and 33% (95% CI, 5%-68%) for the CTRL arm (P = 0.36, 1-sided logrank test). Clinical responses in the INT group were associated with an increase in the prevalence of activated NK cells in their peripheral blood. Conclusions: Ex vivo TKD/IL2-activated, autologous NK cells are well tolerated and deliver positive clinical responses in patients with advanced NSCLC after RCT.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MEMBRANE HEAT-SHOCK-PROTEIN-70 HSP70; LUNG-CANCER; TUMOR-CELLS; NK CELLS; SURFACE; CHEMOTHERAPY; RADIOTHERAPY; CARCINOMA; BLOCKADE; THERAPY; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin Medicine > Lehrstuhl für Strahlentherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Mar 2021 05:58 |
| Last Modified: | 09 Mar 2021 05:58 |
| URI: | https://pred.uni-regensburg.de/id/eprint/43554 |
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