| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Section of Oncology and*
Section of Pathology, Department of Human Pathology and Oncology;
Section of Virology, Department of Molecular Biology;
Giorgio Segre Department of Pharmacology, Siena University School of Medicine, Siena, Italy;
Experimental Oncology Unit, National Cancer Institute of Naples, Fondazione Pascale, Naples, Italy;¶
Medical Oncology and Pharmacology Section, Department of Neuroscience, University of Roma Tor Vergata, Rome, Italy; and||
Experimental Oncology Section, Laboratory of Tumor Immunology and Biology, National Cancer Institute, Bethesda MD 20892
Gemcitabine, oxaliplatin, leucovorin, and 5-fluorouracil (GOLF) is a novel multidrug regimen inducing high levels of necrosis and apoptosis in colon carcinoma cells. This regimen is also able to promote a process of Ag remodeling including up-regulation of immunotherapy targets like carcinoembryonic Ag (CEA), thymidylate synthase (TS). We have conducted a preclinical study aimed to investigate whether these drug-induced modifications would also enhance colon cancer cell immunogenicity. Several CTL lines were thus generated by in vitro stimulating human HLA-A(*)02.01+ PBMCs, from normal donors and colon cancer patients, with autologous dendritic cells cross-primed with cell lysates of colon cancer cells untreated, irradiated, or previously exposed to different drug treatments including the GOLF regimen. Class I HLA-restricted cytolytic activity of these CTL lines was tested against colon cancer cells and CEA and TS gene transfected target cells. These experiments revealed that CTLs sensitized with GOLF-treated cancer cells were much more effective than those sensitized with the untreated colon carcinoma cells or those exposed to the other treatments. CTL lines sensitized against the GOLF-treated colon cancer cells, also expressed a greater percentage of T-lymphocyte precursors able to recognize TS- and CEA-derived peptides. These results suggest that GOLF regimen is a powerful antitumor and immunomodulating regimen that can make the tumor cells a suitable means to induce an Ag-specific CTL response. These results suggest that a rationale combination of GOLF chemotherapy with cytokine-based immunotherapy could generate a chemotherapy-modulated Ag-specific T-lymphocyte response in cancer patients able to destroy the residual disease survived to the cytotoxic drugs.
This article has been cited by other articles:
|
|
 |
|
  S. Buonocore, N. O. Haddou, F. Moore, S. Florquin, F. Paulart, C. Heirman, K. Thielemans, M. Goldman, and V. Flamand Neutrophil-dependent tumor rejection and priming of tumoricidal CD8+ T cell response induced by dendritic cells overexpressing CD95L J. Leukoc. Biol., September 1, 2008; 84(3): 713 - 720. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Correale, P. Tagliaferri, A. Fioravanti, M. T. Del Vecchio, C. Remondo, F. Montagnani, M. S. Rotundo, C. Ginanneschi, I. Martellucci, E. Francini, et al. Immunity Feedback and Clinical Outcome in Colon Cancer Patients Undergoing Chemoimmunotherapy with Gemcitabine + FOLFOX followed by Subcutaneous Granulocyte Macrophage Colony-Stimulating Factor and Aldesleukin (GOLFIG-1 Trial) Clin. Cancer Res., July 1, 2008; 14(13): 4192 - 4199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Bauer, F Bauernfeind, A Sterzik, M Orban, M Schnurr, H A Lehr, S Endres, A Eigler, and M Dauer Dendritic cell-based vaccination combined with gemcitabine increases survival in a murine pancreatic carcinoma model Gut, September 1, 2007; 56(9): 1275 - 1282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. H. Kang, J. H. Lee, C. K. Song, H. D. Han, B. C. Shin, S. I. Pai, C.-F. Hung, C. Trimble, J.-S. Lim, T. W. Kim, et al. Epigallocatechin-3-Gallate Enhances CD8+ T Cell-Mediated Antitumor Immunity Induced by DNA Vaccination Cancer Res., January 15, 2007; 67(2): 802 - 811. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Correale, M. G. Cusi, K. Y. Tsang, M. T. Del Vecchio, S. Marsili, M. L. Placa, C. Intrivici, A. Aquino, L. Micheli, C. Nencini, et al. Chemo-Immunotherapy of Metastatic Colorectal Carcinoma With Gemcitabine Plus FOLFOX 4 Followed by Subcutaneous Granulocyte Macrophage Colony-Stimulating Factor and Interleukin-2 Induces Strong Immunologic and Antitumor Activity in Metastatic Colon Cancer Patients J. Clin. Oncol., December 10, 2005; 23(35): 8950 - 8958. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
