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

Multhoff, G, Seier, S, Stangl, S, Sievert, W, Shevtsov, M, Werner, C, Pockley, AG ORCID: https://orcid.org/0000-0001-9593-6431, Blankenstein, C, Hildebrandt, M, Offner, R, Ahrens, N, Kokowski, K, Hautmann, M, Rödel, C, Fietkau, R, Lubgan, D, Huber, R, Hautmann, H, Duell, T, Molls, M, Specht, H, Haller, B, Devecka, M, Sauter, A and Combs, SE, 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

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Abstract

Purpose: Non–small cell lung cancer (NSCLC) is a fatal disease with poor prognosis. A membrane-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 log-rank test). Clinical responses in the INT group were associated with an increase in the prevalence of activated NK cells in their peripheral blood.

Item Type:	Journal article
Publication Title:	Clinical Cancer Research
Creators:	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., Rödel, C., Fietkau, R., Lubgan, D., Huber, R., Hautmann, H., Duell, T., Molls, M., Specht, H., Haller, B., Devecka, M., Sauter, A. and Combs, S.E.
Publisher:	American Association for Cancer Research (AACR)
Date:	October 2020
Volume:	26
Number:	20
ISSN:	1078-0432
Identifiers:	Number Type 10.1158/1078-0432.ccr-20-1141 DOI 1369967 Other
Rights:	©2020 American Association for Cancer Research.
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	28 Sep 2020 12:28
Last Modified:	31 May 2021 15:07
URI:	https://irep.ntu.ac.uk/id/eprint/40978

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