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Strahlentherapie und Onkologie
Published in: Strahlentherapie und Onkologie 4/2019

Open Access 01-04-2019 | Bronchoscopy | Case Study

Radiochemotherapy combined with NK cell transfer followed by second-line PD-1 inhibition in a patient with NSCLC stage IIIb inducing long-term tumor control: a case study

Authors: Konrad Kokowski, Stefan Stangl, Sophie Seier, Martin Hildebrandt, Peter Vaupel, Gabriele Multhoff

Published in: Strahlentherapie und Onkologie | Issue 4/2019

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Abstract

Background

Membrane heat shock protein 70 (mHsp70) is indicative of high-risk tumors and serves as a tumor-specific target for natural killer (NK) cells stimulated with Hsp70 peptide (TKD) and Interleukin(IL)-2. Radiochemotherapy (RCT), mHsp70-targeting NK cells, and programmed death(PD)-1 inhibition were combined to improve the efficacy of tumor-specific immune cells in a non-small cell lung carcinoma (NSCLC) patient.

Patient

Following simultaneous RCT (64.8 Gy), a patient with inoperable NSCLC (cT4, cN3, cM0, stage IIIb) was treated with 4 cycles of autologous ex vivo TKD/IL-2-activated NK cells and the PD-1 antibody nivolumab as a second-line therapy. Blood samples were taken for immunophenotyping during the course of therapy.

Results

Adoptive transfer of ex vivo TKD/IL-2-activated NK cells after RCT combined with PD-1 blockade is well tolerated and results in superior overall survival (OS). No viable tumor cells but a massive immune cell infiltration in fibrotic tissue was detected after therapy. Neither tumor progression nor distant metastases were detectable by CT scanning 33 months after diagnosis. Therapy response was associated with significantly increased CD3−/NKG2D+/CD94+ NK cell counts, elevated CD8+ to CD4+ T cell and CD3−/CD56bright to CD3−/CD56dim NK cell ratios, and significantly reduced regulatory T cells (Tregs) in the peripheral blood.

Conclusion

A combined therapy consisting of RCT, mHsp70-targeting NK cells, and PD-1 antibody inhibition is well tolerated, induces anti-tumor immunity, and results in long-term tumor control in one patient with advanced NSCLC. Further, randomized studies are necessary to confirm the efficacy of this combination therapy.
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Metadata
Title
Radiochemotherapy combined with NK cell transfer followed by second-line PD-1 inhibition in a patient with NSCLC stage IIIb inducing long-term tumor control: a case study
Authors
Konrad Kokowski
Stefan Stangl
Sophie Seier
Martin Hildebrandt
Peter Vaupel
Gabriele Multhoff
Publication date
01-04-2019
Publisher
Springer Berlin Heidelberg
Published in
Strahlentherapie und Onkologie / Issue 4/2019
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-019-01434-9

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