Radiochemotherapy combined with NK cell transfer followed by second-line PD-1 inhibition in a patient with NSCLC stage IIIb inducing long-term ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-04

AUTHORS

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

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. More... »

PAGES

352-361

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00066-019-01434-9

DOI

http://dx.doi.org/10.1007/s00066-019-01434-9

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112073871

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30747241


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Download the RDF metadata as:  json-ld nt turtle xml License info

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RDF/XML is a standard XML format for linked data.

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273 https://www.grid.ac/institutes/grid.6936.a schema:alternateName Technical University Munich
274 schema:name Department of Radiation Oncology, Klinikum rechts der Isar, TU München (TUM), Munich, Germany
275 Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, TU München (TUM), Munich, Germany
276 Institute of Innovative Radiotherapy (iRT), Department of Radiation Sciences (DRS), Helmholtz Center Munich (HMGU), Munich, Germany
277 Partner site Munich, Deutsches Konsortium für Translationale Krebsforschung (DKTK), Munich, Germany
278 Radiation Immuno-Oncology, Center for Translational Cancer Research TUM (TranslaTUM), Einsteinstr. 25, 81675, Munich, Germany
279 TUMCells, TUM School of Medicine, Munich, Germany
280 rdf:type schema:Organization
 




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