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

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^{−} $/$ CD56^{bright} $ to $ CD3^{−} $/$ CD56^{dim} $ 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..

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:195

Enthalten in:

Strahlentherapie und Onkologie - 195(2019), 4 vom: 11. Feb., Seite 352-361

Sprache:

Englisch

Beteiligte Personen:

Kokowski, Konrad [VerfasserIn]
Stangl, Stefan [VerfasserIn]
Seier, Sophie [VerfasserIn]
Hildebrandt, Martin [VerfasserIn]
Vaupel, Peter [VerfasserIn]
Multhoff, Gabriele [VerfasserIn]

Links:

Volltext [kostenfrei]

BKL:

44.81$jOnkologie

44.64$jRadiologie

Themen:

Adoptive NK cell transfer
Immune checkpoint inhibition
Lung cancer
Membrane Hsp70
Radiotherapy

Anmerkungen:

© The Author(s) 2019

doi:

10.1007/s00066-019-01434-9

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC2096218845

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