Krause, Stefan W, Gastpar, Robert, Andreesen, Reinhard, Gross, Catharina, Ullrich, Heidrun, Thonigs, Gerald, Pfister, Karin and Multhoff, Gabriele
(2004)
Treatment of colon and lung cancer patients with ex vivo heat shock protein 70-peptide-activated, autologous natural killer cells: a clinical phase i trial.
Clinical cancer research : an official journal of the American Association for Cancer Research 10 (11), pp. 3699-707.
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Abstract
PURPOSE: The 14 amino acid sequence (aa(450-463)) TKDNNLLGRFELSG (TKD) of heat shock protein 70 (Hsp70) was identified as a tumor-selective recognition structure for natural killer (NK) cells. Incubation of peripheral blood lymphocyte cells with TKD plus low-dose interleukin 2 (IL-2) enhances the cytolytic activity of NK cells against Hsp70 membrane-positive tumors, in vitro and in vivo. These ...
Abstract
PURPOSE: The 14 amino acid sequence (aa(450-463)) TKDNNLLGRFELSG (TKD) of heat shock protein 70 (Hsp70) was identified as a tumor-selective recognition structure for natural killer (NK) cells. Incubation of peripheral blood lymphocyte cells with TKD plus low-dose interleukin 2 (IL-2) enhances the cytolytic activity of NK cells against Hsp70 membrane-positive tumors, in vitro and in vivo. These data encouraged us to test tolerability, feasibility, and safety of TKD-activated NK cells in a clinical Phase I trial. EXPERIMENTAL DESIGN: Patients with metastatic colorectal cancer (n = 11) and non-small cell lung cancer (n = 1) who had failed standard therapies were enrolled. After ex vivo stimulation of autologous peripheral blood lymphocytes with Hsp70-peptide TKD (2 microg/ml) plus low-dose IL-2 (100 units/ml), TKD was removed by extensive washing, and activated cells were reinfused i.v. The procedure was repeated for up to six cycles, applying a dose escalation schedule in 4 patients. RESULTS: The percentage of activated NK cells in the reinfused leukapheresis products ranged between 8 and 20% of total lymphocytes, corresponding to total NK cell counts of 0.1 up to 1.5 x 10(9). Apart from restless feeling in 1 patient and itching in 2 patients, no negative side effects were observed. Concomitant with an enhanced CD94 cell surface density, the cytolytic activity of NK cells against Hsp70 membrane-positive colon carcinoma cells was enhanced after TKD/IL-2 stimulation in 10 of 12 patients. Concerning tumor response, 1 patient was in stable disease during therapy by formal staging criteria and another patient showed stable disease in one metastases and progression in another. CONCLUSIONS: Reinfusion of Hsp70-activated autologous NK cells is safe. Immunological results warrant additional studies in patients with lower tumor burden.
Export bibliographical data
| Item type: | Article |
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| Date: | 2004 |
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| Institutions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
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| Identification Number: | | Value | Type |
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| 15585648 | PubMed ID | | 10.1158/1078-0432.CCR-03-0683 | DOI |
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| Classification: | | Notation | Type |
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| Adult | MESH | | Aged | MESH | | Antigens, CD/biosynthesis | MESH | | Cell Membrane/metabolism | MESH | | Cell Movement | MESH | | Colonic Neoplasms/therapy | MESH | | Cytotoxicity, Immunologic | MESH | | Disease Progression | MESH | | Female | MESH | | Follow-Up Studies | MESH | | Granzymes | MESH | | HSP70 Heat-Shock Proteins/chemistry | MESH | | Humans | MESH | | Interferon-gamma/blood | MESH | | Interleukin-2/chemistry | MESH | | Killer Cells, Natural/cytology | MESH | | Lectins, C-Type/biosynthesis | MESH | | Lung Neoplasms/therapy | MESH | | Male | MESH | | Middle Aged | MESH | | NK Cell Lectin-Like Receptor Subfamily D | MESH | | Neoplasm Metastasis | MESH | | Phenotype | MESH | | Serine Endopeptidases/blood | MESH | | Time Factors | MESH | | Treatment Outcome | MESH | | Tumor Necrosis Factor-alpha/biosynthesis | MESH |
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| Dewey Decimal Classification: | 600 Technology > 610 Medical sciences Medicine |
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| Status: | Published |
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| Refereed: | Yes, this version has been refereed |
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| Created at the University of Regensburg: | Yes |
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| Item ID: | 14434 |
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