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Multhoff, G., Seier, S., Stangl, S., Sievert, W., Shevtsov, M., Werner, C., Pockley, A.G. 
ORCID: 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, S.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
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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 | ||||||
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| 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 | ||||||
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| 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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