caa a22 4500 469073527 CHVBK 20180323132928.0 cr unu---uuuuu 170328e19920101xx s 000 0 eng 10.1007/BF01741057 doi (NATIONALLICENCE)springer-10.1007/BF01741057 Chemo-Immunotherapy of murine solid tumors: Enhanced therapeutic effects by interleukin-2 combined with interferon α and the role of specific T cells [Elektronische Daten] [Eli Kedar, Yaron Rutkowski, Benny Leshem] Summary: The aim of the present study has been to assess the therapeutic efficacy of various cytokines, singly or in combination, with and without chemotherapy (cyclophosphamide, Cy), in mice carrying advanced, weakly immunogenic tumors (MCA-105 sarcoma, M109 carcinoma). Treatment of animals with i.p. growths or experimental pulmonary metastases began 8-18 days after i.p. or i.v. tumor cell inoculation respectively. None of the cytokines tested [interleukin-2 (IL-2), interferon α (IFNα), tumor necrosis factor α (TNFα) and macrophage-colony-stimulating factor (M-CSF)] nor Cy had by itself a significant curative effect. A synergistic therapeutic effect was obtained with IL-2 or IFNα (but not with TNFα or M-CSF) in combination with Cy. The most efficacious regimen (65%-90% cure of mice carrying i.p. tumors) was the combination of Cy+IL-2+IFNα. Preliminary experiments suggested that sequential administration of these cytokines might be more beneficial than concurrent administration. Following successful immunotherapy, long-term (3-6 months) survivors showed a tumor-specific resistance to a second tumor challenge and their spleen contained an increased number of specific antitumor cytotoxic T lymphocyte precursors (5- to 20-fold, compared to control mice). In vitro and in vivo cell-depletion experiments using monoclonal antibodies revealed that T cells (primarily CD8), but not NK cells, are crucial for the therapeutic effects. This study indicates that a potent specific antitumor T cell immunity can be elicited against advanced weakly immunogenic tumors by combining chemotherapy (Cy) with IL-2 and IFNα. Springer-Verlag, 1992 Chemo-immunotherapy nationallicence Cytokines nationallicence T cells nationallicence Kedar Eli The Lautenberg Center for General and Tumor Immunology, The Hebrew University — Hadassah Medical School, 91010, Jerusalem, Israel aut Rutkowski Yaron The Lautenberg Center for General and Tumor Immunology, The Hebrew University — Hadassah Medical School, 91010, Jerusalem, Israel aut Leshem Benny The Lautenberg Center for General and Tumor Immunology, The Hebrew University — Hadassah Medical School, 91010, Jerusalem, Israel aut Cancer Immunology, Immunotherapy Springer-Verlag 35/1(1992-01-01), 63-68 0340-7004 35:1<63 1992 35 262 https://doi.org/10.1007/BF01741057 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01741057 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kedar Eli The Lautenberg Center for General and Tumor Immunology, The Hebrew University — Hadassah Medical School, 91010, Jerusalem, Israel aut NATIONALLICENCE 700 1- Rutkowski Yaron The Lautenberg Center for General and Tumor Immunology, The Hebrew University — Hadassah Medical School, 91010, Jerusalem, Israel aut NATIONALLICENCE 700 1- Leshem Benny The Lautenberg Center for General and Tumor Immunology, The Hebrew University — Hadassah Medical School, 91010, Jerusalem, Israel aut NATIONALLICENCE 773 0- Cancer Immunology, Immunotherapy Springer-Verlag 35/1(1992-01-01), 63-68 0340-7004 35:1<63 1992 35 262 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer