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Milani, V. ; Stangl, S.* ; Issels, R.D. ; Gehrmann, M.* ; Wagner, B.* ; Hube, K.* ; Mayr, D. ; Hiddemann, W. ; Molls, M.* ; Multhoff, G.

Anti-tumor activity of patient-derived NK cells after cell-based immunotherapy - a case report.

J. Transl. Med. 7:50 (2009)
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Background: Membrane-bound heat shock protein 70 (Hsp70) serves as a tumor-specific recognition structure for Hsp70-peptide (TKD) plus IL-2 activated NK cells. A phase I clinical trial has shown that repeated re-infusions of ex vivo TKD/IL-2-activated, autologous leukapheresis product is safe. This study investigated the maintenance of the cytolytic activity of NK cells against K562 cells and autologous tumor after 6 plus 3 infusions of TKD/IL-2-activated effector cells. Methods: A stable tumor cell line was generated from the resected anastomotic relapse of a patient with colon carcinoma (pT3, N2, M0, G2). Two months after surgery, the patient received the first monthly i.v. infusion of his ex vivo TKD/IL-2-activated peripheral blood mononuclear cells (PBMNC). After 6 infusions and a pause of 3 months, the patient received another 3 cell infusions. The phenotypic characteristics and activation status of tumor and effector cells were determined immediately before and at times after each infusion. Results: The NK cell ligands Hsp70, MICA/B, and ULBP-1,2,3 were expressed on the patient's anastomotic relapse. An increased density of activatory NK cell receptors following ex vivo stimulation correlated with an enhanced anti-tumoricidal activity. After 4 re-infusion cycles, the intrinsic cytolytic activity of non-stimulated PBMNC was significantly elevated and this heightened responsiveness persisted for up to 3 months after the last infusion. Another 2 re-stimulations with TKD/IL-2 restored the cytolytic activity after the therapeutic pause. Conclusion: In a patient with colon carcinoma, repeated infusions of ex vivo TKD/IL-2-activated PBMNC initiate an intrinsic NK cell-mediated cytolytic activity against autologous tumor cells.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter NATURAL-KILLER-CELLS; HEAT-SHOCK PROTEINS; III COLON-CANCER; SEVERE COMBINED IMMUNODEFICIENCY; COLORECTAL-CANCER; TUMOR-CELLS; CYTOLYTIC ACTIVITY; ADJUVANT THERAPY; LIVER METASTASES; LEUKEMIC BLASTS
Sprache englisch
Veröffentlichungsjahr 2009
HGF-Berichtsjahr 0
ISSN (print) / ISBN 1479-5876
e-ISSN 1479-5876
Zeitschrift Journal of Translational Medicine
Quellenangaben Band: 7, Heft: , Seiten: , Artikelnummer: 50 Supplement: ,
Verlag BioMed Central
Begutachtungsstatus Peer reviewed
Institut(e) CCG Innate Immunity in Tumor Biology (PATH-KTB)
CCG Tumor Therapy with Hyperthermia (IMI-KTH)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er)
Immune Response and Infection
PSP-Element(e) G-521400-001
G-521100-001
PubMed ID 19549307
DOI 10.1186/1479-5876-7-50
WOS ID 000268204100001
Scopus ID 68349100013
Erfassungsdatum 2009-09-03
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