Hennemann, Burkhard and Beckmann, Gabriele and Eichelmann, Annette and Rehm, Annegret and Andreesen, Reinhard (1998) Phase I trial of adoptive immunotherapy of cancer patients using monocyte-derived macrophages activated with interferon gamma and lipopolysaccharide. CANCER IMMUNOLOGY IMMUNOTHERAPY, 45 (5). pp. 250-256. ISSN 0340-7004,
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Cells of the monocyte/macrophage lineage have shown antitumor activity in vitro and in murine models after activation with interferon (IFN) gamma. In vitro data suggest an additional effect on macrophage antitumor activity when IFN gamma is combined with endotoxin (lipopolysaccharides; LPS). In this study we treated nine cancer patients with a total of 62 MAK infusion cycles with autologous macrophages given intravenously (i.v.) after in vitro activation with IFN gamma and LPS. Low-grade fever (WHO I/II) was the commonest side-effect. Chills, nausea, and headache were noted when the number of transfused macrophages exceeded 2x10(8). One WHO IV toxicity occurred, consisting of hypotension after transfer of 3x10(8) cells, defining this dose as the maximum cell number tolerated. After pretreatment with ibuprofen, however, the maximum cell number could be increased without reaching dose-limiting toxicity. The highest number of cells reinfused was 15x10(8). Circulating interleukin(IL)-6 increased in a dose-dependent manner as did IL-1 receptor antagonist (IL-1RA) and IL-8. Tumor response consisted of one case of stable disease (12 weeks) in a patient with formerly progressing colorectal cancer and progressive diseases in eight patients. This study indicates that reinfusion of autologous LPS-activated macrophages upon pretreatment with ibuprofen is feasible and tolerated without major side-effects.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BLOOD MONOCYTES; MATURATION; INVITRO; CELL; PERSPECTIVES; EXPRESSION; ENDOTOXIN; immunotherapy; monocytes/macrophages; interferon gamma; endotoxin; lipopolysaccharides |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Oct 2023 09:39 |
| Last Modified: | 24 Oct 2023 09:39 |
| URI: | https://pred.uni-regensburg.de/id/eprint/50174 |
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