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Multhoff, G.* ; Seier, S.* ; Stangl, S.* ; Sievert, W.* ; Shevtsov, M.* ; Werner, C.* ; Pockley, A.G.* ; Blankenstein, C.* ; Hildebrandt, M.* ; Offner, R.* ; Ahrens, N.* ; Kokowski, K.* ; Hautmann, M.* ; Roedel, C.* ; Fietkau, R.* ; Lubgan, D.* ; Huber, R.* ; Hautmann, H.* ; Duell, T.* ; Molls, M.* ; Specht, H.* ; Haller, B.* ; Devecka, M.* ; Sauter, A.* ; Combs, S.E.

Targeted natural killer cell-based adoptive immunotherapy for the treatment of patients with NSCLC after radiochemotherapy: A randomized phase II clinical trial.

Clin. Cancer Res. 26, 5368-5379 (2020)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Membrane Heat-shock-protein-70 Hsp70; Lung-cancer; Tumor-cells; Nk Cells; Surface; Chemotherapy; Radiotherapy; Carcinoma; Blockade; Therapy
ISSN (print) / ISBN 1078-0432
e-ISSN 1557-3265
Quellenangaben Volume: 26, Issue: 20, Pages: 5368-5379 Article Number: , Supplement: ,
Publisher American Association for Cancer Research (AACR)
Publishing Place 615 Chestnut St, 17th Floor, Philadelphia, Pa 19106-4404 Usa
Reviewing status Peer reviewed
Grants DFG-STA1520/1-1
multimmune GmbH
German Research Foundation (DFG)
BMWi (AiF-roject GmbH)
BMBF "Kompetenzverbund Strahlenforschung"
BMBF "Innovative Therapies"