TY - JOUR
T1 - Anti-tumor activity of patient-derived NK cells after cell-based immunotherapy - A case report
AU - Milani, Valeria
AU - Stangl, Stefan
AU - Issels, Rolf
AU - Gehrmann, Mathias
AU - Wagner, Beate
AU - Hube, Kathrin
AU - Mayr, Doris
AU - Hiddemann, Wolfgang
AU - Molls, Michael
AU - Multhoff, Gabriele
N1 - Funding Information:
This work was supported in part by grants from the Deutsche Forschungs-gemeinschaft (DFG MU1238 7/2), the Bundesministerium für Forschung und Technologie (BMBF, BioChance Plus, MOBITUM), EU-CARDIORISK (#211403), EU-STEMDIAGNOSTICS (#037703), EU-TRANSNET (#512253), and the multimmune GmbH, Munich.
PY - 2009/6/23
Y1 - 2009/6/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=68349100013&partnerID=8YFLogxK
U2 - 10.1186/1479-5876-7-50
DO - 10.1186/1479-5876-7-50
M3 - Article
C2 - 19549307
AN - SCOPUS:68349100013
SN - 1479-5876
VL - 7
JO - Journal of Translational Medicine
JF - Journal of Translational Medicine
M1 - 50
ER -