Navegar

Colección

Datos Estadísticas

Artículo

Este artículo es de Acceso Abierto y puede ser descargado en su versión final desde nuestro repositorio
Consulte el artículo en la página del editor
Consulte la política de Acceso Abierto del editor

Abstract:

Background: Sixteen melanoma patients (1 stage IIC, 8 stage III, and 7 stage IV) were treated in a Phase I study with a vaccine (DC/Apo-Nec) composed of autologous dendritic cells (DCs) loaded with a mixture of apoptotic/necrotic allogeneic melanoma cell lines (Apo-Nec), to evaluate toxicity and immune responses. Also, IL-10 1082 genotype was analyzed in an effort to predict disease progression. Methods: PBMC were obtained after leukapheresis and DCs were generated from monocytes cultured in the presence of GM-CSF and IL-4 in serum-free medium. Immature DCs were loaded with gamma-irradiated Apo-Nec cells and injected id without adjuvant. Cohorts of four patients were given four vaccines each with 5, 10, 15, or 20 × 106 DC/Apo-Nec cell per vaccine, two weeks apart. Immune responses were measured by ELISpot and tetramer analysis. Il-10 genotype was measured by PCR and corroborated by IL-10 production by stimulated PBMC. Results: Immature DCs efficiently phagocytosed melanoma Apo-Nec cells and matured after phagocytosis as evidenced by increased expression of CD83, CD80, CD86, HLA class I and II, and 75.2 ± 16% reduction in Dextran-FITC endocytosis. CCR7 was also up-regulated upon Apo-Nec uptake in DCs from all patients, and accordingly DC/Apo-Nec cells were able to migrate in vitro toward MIP-3 beta. The vaccine was well tolerated in all patients. The DTH score increased significantly in all patients after the first vaccination (Mann-Whitney Test, p < 0.05). The presence of CD8+T lymphocytes specific to gp100 and Melan A/ MART-1 Ags was determined by ELISpot and tetramer analysis in five HLA-A*0201 patients before and after vaccination; one patient had stable elevated levels before and after vaccination; two increased their CD8 + levels, one had stable moderate and one had negligible levels. The analysis of IL-10 promoter -1082 polymorphism in the sixteen patients showed a positive correlation between AA genotype, accompanied by lower in vitro IL-10 production by stimulated PBMC, and faster melanoma progression after lymph nodes surgery (p = 0.04). With a mean follow-up of 49.5 months post-surgery, one stage IIC patient and 7/8 stage III patients remain NED but 7/7 stage IV patients have progressed. Conclusion: We conclude that DC/Apo-Nec vaccine is safe, well tolerated and it may induce specific immunity against melanoma Ags. Patients with a low-producing IL-10 polymorphism appear to have a worst prognosis. © 2008 von Euw et al; licensee BioMed Central Ltd.

Registro:

Documento: Artículo
Título:A phase I clinical study of vaccination of melanoma patients with dendritic cells loaded with allogeneic apoptotic/necrotic melanoma cells. Analysis of toxicity and immune response to the vaccine and of IL-10-1082 promoter genotype as predictor of disease progression
Autor:von Euw, E.M.; Barrio, M.M.; Furman, D.; Levy, E.M.; Bianchini, M.; Peguillet, I.; Lantz, O.; Vellice, A.; Kohan, A.; Chacón, M.; Yee, C.; Wainstok, R.; Mordoh, J.
Filiación:Centro de Investigaciones Oncológicas FUCA, Cramer 1180, 1426 Buenos Aires, Argentina
Laboratorio de Cancerología, Fundación Instituto Leloir, IIBA -CONICET, Patricias Argentinas, 1405 Buenos Aires, Argentina
Laboratoire d'Immunologie, Institut Curie, 26 rue d'Ulm, 75005 Paris, France
Unité Inserm 653, Institut Curie, 26 rue d'Ulm, 75005 Paris, France
Instituto Médico Alexander Fleming, Cramer 1180, 1426 Buenos Aires, Argentina
Fred Hutchinson Cancer Research Centre, Clinical Research Division, 1100 Fairview Avenue N., Seattle, WA 98109-1024, United States
Departamento Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:alpha interferon; B7 antigen; CD8 antigen; CD83 antigen; CD86 antigen; chemokine receptor CCR7; dendritic cell vaccine; dextran; fluorescein isothiocyanate; glycoprotein gp 100; granulocyte macrophage colony stimulating factor; HLA A antigen; HLA antigen class 1; HLA antigen class 2; interleukin 10; interleukin 4; macrophage inflammatory protein 3beta; melan A; melanoma antigen; tetramer; cancer vaccine; interleukin 10; abdominal cramp; abdominal pain; adolescent; adult; anorexia; antigen expression; apoptosis; article; asthenia; cancer staging; CD8+ T lymphocyte; cell culture; cell death; cell maturation; cell migration; cell stimulation; chill; clinical trial; controlled clinical trial; controlled study; correlation analysis; culture medium; cytokine production; dendritic cell; diarrhea; disease course; drug safety; drug tolerability; endocytosis; enzyme linked immunospot assay; fatigue; female; follow up; gamma radiation; genetic polymorphism; genotype; headache; human; human cell; humoral immunity; immune response; in vitro study; injection site reaction; leukapheresis; liver dysfunction; lymph node dissection; lymphocyte proliferation; male; melanoma; melanoma cell; monocyte; myalgia; nausea; peripheral blood mononuclear cell; phagocytosis; phase 1 clinical trial; polymerase chain reaction; prediction; prognosis; promoter region; treatment outcome; tumor immunity; upregulation; vomiting; autotransplantation; delayed hypersensitivity; dendritic cell; genetics; immunology; lymphocyte activation; melanoma; middle aged; necrosis; pathology; patient selection; prediction and forecasting; transplantation; Adolescent; Adult; Apoptosis; Cancer Vaccines; Dendritic Cells; Disease Progression; Female; Genotype; Humans; Hypersensitivity, Delayed; Interleukin-10; Lymphocyte Activation; Male; Melanoma; Middle Aged; Necrosis; Neoplasm Staging; Patient Selection; Phagocytosis; Polymorphism, Genetic; Predictive Value of Tests; Promoter Regions (Genetics); Transplantation, Autologous
Año:2008
Volumen:6
DOI: http://dx.doi.org/10.1186/1479-5876-6-6
Título revista:Journal of Translational Medicine
Título revista abreviado:J. Transl. Med.
ISSN:14795876
CAS:chemokine receptor CCR7, 231617-75-7; dextran, 87915-38-6, 9014-78-2; fluorescein isothiocyanate, 25168-13-2, 27072-45-3, 3326-32-7; macrophage inflammatory protein 3beta, 181030-14-8; Cancer Vaccines; Interleukin-10, 130068-27-8
PDF:https://bibliotecadigital.exactas.uba.ar/download/paper/paper_14795876_v6_n_p_vonEuw.pdf
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14795876_v6_n_p_vonEuw

Referencias:

  • Greenlee, R.T., Murray, T., Bolden, S., Wingo, P.A., Cancer statistics, 2000 (2000) CA Cancer J Clin, 50 (1), pp. 7-33. , 10735013
  • Kirkwood, J.M., Manola, J., Ibrahim, J., Sondak, V., Ernstoff, M.S., Rao, U., A Pooled Analysis of Eastern Cooperative Oncology Group and Intergroup Trials of Adjuvant High-Dose Interferon for Melanoma (2004) Clin Cancer Res, 10, pp. 1670-1677. , 10.1158/1078-0432.CCR-1103-3 15014018
  • Koebel, C.M., Vermi, W., Swann, J.B., Zerafa, N., Rodig, S.J., Old, L.J., Smyth, M.J., Schreiber, R.D., Adaptive immunity maintains occult cancer in an equilibrium state (2007) Nature, 6 (7171), pp. 903-907. , 450 10.1038/nature06309
  • Smyth, M.J., Dunn, G.P., Schreiber, R.D., Cancer immunosurveillance and immunoediting: The roles of immunity in suppressing tumor development and shaping tumor immunogenicity (2006) Adv Immunol, 90, pp. 1-50. , 10.1016/S0065-2776(06)90001-7 16730260
  • Schuler, G., Steinman, R.M., Dendritic cells as adjuvants for immune-mediated resistance to tumors (1997) J Exp Med, 186, pp. 1183-1187. , 10.1084/jem.186.8.1183 9379142
  • Banchereau, J., Steinman, R.M., Dendritic cells and the control of immunity (1998) Nature, 392, pp. 245-252. , 10.1038/32588 9521319
  • Kawakami, Y., Eliyahu, S., Delgado, C.H., Robbins, P.F., Sakaguchi, K., Appella, E., Yannelli, J.R., Rosenberg, S.A., Identification of a human melanoma antigen recognized by tumor-infiltrating lymphocytes associated with in vivo tumor rejection (1994) Proc Natl Acad Sci USA, 91, pp. 6458-6462. , 44221 8022805 10.1073/pnas.91.14.6458
  • Kawakami, Y., Eliyahu, S., Jennings, C., Sakaguchi, K., Kang, X., Southwood, S., Robbins, P.F., Rosenberg, S.A., Recognition of multiple epitopes in the human melanoma antigen gp100 by tumor-infiltrating T lymphocytes associated with in vivo tumor regression (1995) J Immunol, 154, pp. 3961-3968. , 7706734
  • Brasseur, F., Rimoldi, D., Liénard, D., Lethé, B., Carrel, S., Arienti, F., Suter, L., Marchand, M., Expression of MAGE genes in primary and metastatic cutaneous melanoma (1995) Int J Cancer, 63, pp. 375-380. , 10.1002/ijc.2910630313 7591235
  • Brichard, V., Van Pel, A., Wolfel, T., Wolfel, C., De Plaen, E., Lethe, B., Coulie, P., Boon, T., The tyrosinase gene codes for an antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas (1993) J Exp Med, 178, pp. 489-495. , 10.1084/jem.178.2.489 8340755
  • Wang, R.F., Appella, E., Kawakami, Y., Kang, X., Rosenberg, S.A., Identification of TRP-2 as a human tumor antigen recognized by cytotoxic T lymphocytes (1996) J Exp Med, 184, pp. 2207-2216. , 10.1084/jem.184.6.2207 8976176
  • Cheresh, D.A., Harper, J.R., Schulz, G., Reisfeld, R.A., Localization of the gangliosides GD2 and GD3 in adhesion plaques and on the surface of human melanoma cells (1984) Proc Natl Acad Sci USA, 81, pp. 5767-5771. , 10.1073/pnas.81.18.5767 6385004 391792
  • Valmori, D., Dutoit, V., Lienard, D., Rimoldi, D., Pittet, M.J., Champagne, P., Ellefsen, K., Romero, P., Naturally occurring human lymphocyte antigen-A2 restricted CD8+ T-cell response to the cancer testis antigen NY-ESO-1 in melanoma patients (2000) Cancer Res, 60, pp. 4499-4506. , 10969798
  • Schadendorf, D., Ugurel, S., Schuler-Thurner, B., Nestle, F.O., Enk, A., Bröcker, E.B., Grabbe, S., Schuler, G., Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: A randomized phase III trial of the DC study group of the DeCOG (2006) Ann Oncol, 17 (4), pp. 563-570. , study group of the DeCOG 10.1093/annonc/mdj138 16418308
  • Salcedo, M., Bercovici, N., Taylor, R., Vereecken, P., Massicard, S., Duriau, D., Vernel-Pauillac, F., Velu, T., Vaccination of melanoma patients using dendritic cells loaded with an allogeneic tumor cell lysate (2005) Cancer Immunol Immunother, 55 (7), pp. 819-829. , 10.1007/s00262-005-0078-6 16187085
  • Palucka, A.K., Ueno, H., Connolly, J., Kerneis-Norvell, F., Blanck, J.P., Johnston, D.A., Fay, J., Banchereau, J., Dendritic cells loaded with killed allogeneic melanoma cells can induce objective clinical responses and MART-1 specific CD8+ T-cell immunity (2006) J Immunother, 29, pp. 545-557. , 10.1097/01.cji.0000211309.90621.8b 16971810
  • Goldszmid, R.S., Idoyaga, J., Bravo, A.I., Steinman, R., Mordoh, J., Wainstok, R., Dendritic cells charged with apoptotic tumor cells induce long-lived protective CD4+ and CD8+ T cell immunity against B16 melanoma (2003) J Immunol, 171, pp. 5940-5947. , 14634105
  • Blachere, N.E., Darnell, R.B., Albert, M.L., Apoptotic cells deliver processed antigen to dendritic cells for cross-presentation (2005) PLoS Biol, 3, pp. e185. , 1084338 15839733 10.1371/journal.pbio.0030185
  • Chen, Z., Moyana, T., Saxena, A., Warrington, R., Jia, Z., Xiang, J., Efficient antitumor immunity derived from maturation of dendritic cells that had phagocytosed apoptotic/necrotic tumor cells (2001) Int J Cancer, 93, pp. 539-548. , 10.1002/ijc.1365 11477558
  • Thumann, P., Moc, I., Humrich, J., Berger, T.G., Schultz, E.S., Schuler, G., Jenne, L., Antigen loading of dendritic cells with whole tumor cel preparations (2003) J Immunol Methods, 277, pp. 1-16. , 10.1016/S0022-1759(03)00102-9 12799035
  • von Euw, E.M., Barrio, M.M., Furman, D., Bianchini, M., Levy, E.M., Yee, C., Li, Y., Mordoh, J., Monocyte-derived dendritic cells loaded with a mixture of apoptotic/ necrotic melanoma cells efficiently cross-present gp100 and MART-1 antigens to specific CD8+ T lymphocytes (2007) J Transl Med, 5, p. 19. , 1863425 17448240 10.1186/1479-5876-5-19
  • Nikolova, P.N., Pawelec, G.P., Mihailova, S.M., Ivanova, M.I., Myhailova, A.P., Baltadjieva, D.N., Marinova, D.I., Naumova, E.J., Association of cytokine gene polymorphisms with malignant melanoma in Caucasian population (2007) Cancer Immunol Immunother, 56, pp. 371-379. , 10.1007/s00262-006-0193-z 16835788
  • Vuoristo, M.S., The polymorphisms of interleukin-10 gene influence the prognosis of patients with advanced melanoma (2007) Cancer Genet Cytogenet, 176, pp. 54-57. , 10.1016/j.cancergencyto.2007.03.002 17574964
  • Howell, W.M., Rose-Zerilli, M.J., Cytokine gene polymorphisms, cancer susceptibility, and prognosis (2007) J Nutr, 137, pp. 194S-199S. , 17182825
  • Turner, D.M., Williams, D.M., Sankaran, D., Lazarus, M., Sinnott, P.J., Hutchinson, I.V., An investigation of polymorphism in the interleukin-10 gene promoter (1997) Eur J Immunogenet, 24, pp. 1-8. , 9043871
  • Mocellin, S., Panelli, M.C., Wang, E., Nagorsen, D., Marincola, F.M., The dual role of IL-10 (2003) Trends Immunol, 24, pp. 36-43. , 10.1016/S1471-4906(02)00009-1 12495723
  • Kohno, T., Mizukami, H., Suzuki, M., Saga, Y., Takei, Y., Shimpo, M., Matsushita, T., Ozawa, K., Interleukin-10-mediated inhibition of angiogenesis and tumor growth in mice bearing VEGF-producing ovarian cancer (2003) Cancer Res, 63, pp. 5091-5094. , 12941839
  • Ruegg, C., Hasmim, M., Lejeune, F.J., Alghisia, G.C., Antiangiogenic peptides and proteins: From experimental tools to clinical drugs (2006) Biochimica Et Biophysica Acta Reviews on Cancer, 1765, pp. 155-177. , 10.1016/j.bbcan.2005.09.003
  • Hamburger, A.W., The human tumor clonogenic assay as a model system in cell biology (1987) Inter J Cell Cloning, 5, pp. 89-107
  • Yee, C., Thompson, J.A., Byrd, D., Riddell, S.R., Roche, P., Celis, E., Greenberg, P.D., Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: In vivo persistence, migration, and antitumor effect of transferred T cells (2002) Proc Natl Acad Sci USA, 99, pp. 16168-16173. , 138583 12427970 10.1073/pnas.242600099
  • Barrio, M.M., Tshurl de Motta, P., Kaplan, P., von Euw, E.M., Bravo, A.I., Chacón, R.D., Mordoh, J., A Phase I Study Of An Allogeneic Cell Vaccine (Vaccimel) with GM-SF In Melanoma Patients (2006) J Immunother, 29 (4), pp. 444-454. , 10.1097/01.cji.0000208258.79005.5f 16799340
  • Lowry, O.H., Rosebrough, N.J., Farr, A.L., Randall, R.J., Protein measurement with the Folin phenol reagent (1951) J Biol Chem, 193, pp. 265-275. , 14907713
  • Bover, L., Barrio, M.M., Slavutsky, I., Bravo, A.I., Quintans, C., Bagnati, A., Lema, B., Mordoh, J., Description of a new human breast cancer cell line, IIB-BR-G, established from a primary undifferentiated tumor (1991) Breast Cancer Res and Treat, 19, pp. 47-56. , 10.1007/BF01975204
  • Doyle, J.J., Doyle, J.L., A rapid DNA isolation procedure for small quantities of fresh leaf tissue (1987) Phytochemistry Bulletin, 19, pp. 11-15
  • Marka, M., Bessenyei, B., Zeher, M., Semsei, I., IL-10 promoter -1082 polymorphism is associated with elevated IL-10 levels in control subjects but does not explain elevated plasma IL-10 observed in Sjogren's syndrome in a Hungarian cohort (2005) Scand J Immunol, 62, pp. 474-480. , 10.1111/j.1365-3083.2005.01675.x 16305644
  • Stanilova, S.A., Miteva, L.D., Karakolev, Z.T., Stefanov, C.S., Interleukin-10-1082 promoter polymorphism in association with cytokine production and sepsis susceptibility (2006) Intensive Care Med, 32, pp. 260-266. , 10.1007/s00134-005-0022-4 16435103
  • Martinez-Escribano, J.A., Moya-Quiles, M.R., Muro, M., Montes-Ares, O., Hernandez-Caselles, T., Frias, J.F., Alvarez-Lopez, M.R., Interleukin-10, interleukin-6 and interferon-gamma gene polymorphisms in melanoma patients (2002) Melanoma Res, 12 (5), pp. 465-469. , 10.1097/00008390-200209000-00008 12394188
  • Alonso, R., Suarez, A., Castro, P., Lacave, A.J., Gutierrez, C., Influence of interleukin-10 genetic polymorphism on survival rates in melanoma parients with advanced disease (2004) Melanoma Res, 15, pp. 53-60. , 10.1097/00008390-200502000-00009
  • De Vries, I.J., Lesterhuis, W.J., Scharenborg, N.M., Engelen, L.P., Ruiter, D.J., Gerritsen, M.J., Croockewitt, S., Punt, C.J., Maturation of dendritic cells is a prerequisite for inducing immune responses in advanced melanoma patients (2003) Clin Cancer Res, 9 (14), pp. 5091-5100. , 14613986
  • Adams, S., O'Neill, D., Bjardwaj, N., Maturation matters: Importance of maturation for antitumor immunity of dendritic cell vaccines (2004) J Clin Oncol, 22, pp. 3834-3835. , 10.1200/JCO.2004.99.019 15365084
  • Neves, A.R., Ensina, L.F., Anselmo, L.B., Leite, K.R., Buzaid, A.C., Câmara-Lopes, L.H., Barbuto, J.A., Dendritic cells derived from metastatic cancer patients vaccinated with allogeneic dendritic cell-autologous tumor cell hybrids express more CD86 and induce higher levels of interferon-gamma in mixed lymphocyte reactions (2005) Cancer Immunol Immunother, 54 (1), pp. 61-66. , 10.1007/s00262-004-0550-8 15693140
  • Baars, A., Claessen, A.M., van den Eertwegh, A.J., Gall, H.E., Stam, A.G., Meijer, S., Giaccone, G., Pinedo, H.M., Skin tests predict survival after autologous tumor cell vaccination in metastatic melanoma: Experience in 81 patients (2000) Ann Oncol, 11 (8), pp. 965-970. , 10.1023/A:1008363601515 11038032
  • Escobar, A., López, M., Serrano, A., Ramirez, M., Pérez, C., Aguirre, A., González, R., Salazar-Onfray, F., Dendritic cell immunizations alone or combined with low doses of interleukin-2 induce specific immune responses in melanoma patients (2005) Clin Exp Immunol, 142 (3), pp. 555-568. , 1809550 16297169
  • Tuettenberg, A., Becker, C., Huter, E., Knop, J., Enk, A.H., Jonuleit, H., Induction of strong and persistent MelanA/MART-1-specific immune responses by adjuvant dendritic cell-based vaccination of stage II melanoma patients (2006) Int J Cancer, 118, pp. 2617-2627. , 10.1002/ijc.21679 16353138
  • Rivoltini, L., Kawakami, Y., Sakaguchi, K., Southwood, S., Sette, A., Robbins, P.F., Marincola, F.M., Rosenberg, S.A., Induction of tumor-reactive CTL from peripheral blood and tumor-infiltrating lymphocytes of melanoma patients by in vitro stimulation with an immunodominant peptide of the human melanoma antigen MART-1 (1995) J Immunol, 154, pp. 2257-2265. , 7868898
  • Berset, M., Cerottini, J.P., Guggisber, D., Romero, P., Burri, F., Rimoldi, D., Panizzon, R.G., Expression of Melan-A/MART-1 antigen as a prognostic factor in primary cutaneous melanoma (2001) Int J Cancer, 95, pp. 73-77. , 10.1002/1097-0215(20010120)95:1<73::AID-IJC1013>3.0.CO;2-S 11241315
  • Clemons-Miller, A.R., Chatta, G.S., Hutchins, L., Angtuaco, E.J., Ravaggi, A., Santin, A.D., Cannon, M.J., Intrathecal cytotoxic T-cell immunotherapy for metastatic leptomeningeal melanoma (2001) Clin Cancer Res, 7 (3 SUPPL.), pp. 917s-924s. , 11300492
  • Speiser, D.E., Pittet, M.J., Rimoldi, D., Guillaume, P., Luescher, I.F., Lienard, D., Lejeune, F., Romero, P., Evaluation of melanoma vaccines with molecularly defined antigens by ex vivo monitoring of tumor-specific T cells (2003) Semin Cancer Biol, 13 (6), pp. 461-472. , 10.1016/j.semcancer.2003.09.010 15001165
  • Schaed, S.G., Klimek, V.M., Panageas, K.S., Musselli, C.M., Butterworth, L., Hwu, W.J., Livingston, P.O., Chapman, P.B., T-cell responses against tyrosinase 368-376(370D) peptide in HLA*A0201+ melanoma patients: Randomized trial comparing incomplete Freund's adjuvant, granulocyte macrophage colony-stimulating factor, and QS-21 as immunological adjuvants (2002) Clin Cancer Res, 8 (5), pp. 967-972. , 12006508
  • Appay, V., Rowland-Jones, S.L., Lessons from the study of T-cell differentiation in persistent human virus infection (2004) Semin Immunol, 16 (3), pp. 205-212. , 10.1016/j.smim.2004.02.007 15130505
  • Goepfert, P.A., Bansal, A., Edwards, B.H., Ritter Jr., G.D., Tellez, I., McPherson, S.A., Sabbaj, S., Mulligan, M.J., A significant number of human immunodeficiency virus epitope-specific cytotoxic T lymphocytes detected by tetramer binding do not produce gamma interferon (2000) J Virol, 74 (21), pp. 10249-10255. , 102068 11024158 10.1128/JVI.74.21.10249-10255.2000
  • Tan, L.C., Gudgeon, N., Annels, N.E., Hansasuta, P., O'Callaghan, C.A., Rowland-Jones, S., McMichael, A.J., Callan, M.F., A re-evaluation of the frequency of CD8+ T cells specific for EBV in healthy virus carriers J Immunol, 162 (3), pp. 1827-1835. , 1999 Feb 1 9973448
  • Lee, P.P., Yee, C., Savage, P.A., Fong, L., Brockstedt, D., Weber, J.S., Johnson, D., Davis, M.M., Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients (1999) Nat Med, 5 (6), pp. 677-685. , 10.1038/9525 10371507
  • Appay, V., Jandus, C., Voelter, V., Reynard, S., Coupland, S.E., Rimoldi, D., Lienard, D., Speiser, D.E., New generation vaccine induces effective melanoma-specific CD8+ T cells in the circulation but not in the tumor site (2006) J Immunol, 177 (3), pp. 1670-1678. , 16849476
  • Zou, W., Immunosuppressive networks in the tumour environment and their therapeutic relevance (2005) Nat Rev Cancer, 5 (4), pp. 263-274. , 10.1038/nrc1586 15776005
  • McCarron, S.L., Edwards, S., Evans, P.R., Gibbs, R., Dearnaley, D.P., Dowe, A., Southgate, C., Howell, W.M., Influence of cytokine gene polymorphisms on the development of prostate cancer (2002) Cancer Res, 62 (12), pp. 3369-3372. , 12067976
  • Havranek, E., Howell, W.M., Fussell, H.M., Whelan, J.A., Whelan, M.A., Pandha, H.S., An interleukin-10 promoter polymorphism may influence tumor development in renal cell carcinoma (2005) J Urol, 173 (3), pp. 709-712. , 10.1097/01.ju.0000152493.86001.91 15711248
  • Howell, W.M., Rose-Zerilli, M.J., Cytokine gene polymorphisms, cancer susceptibility, and prognosis (2007) J Nutr, 137 (1 SUPPL.), pp. 194S-199S. , 17182825

Citas:

---------- APA ----------
von Euw, E.M., Barrio, M.M., Furman, D., Levy, E.M., Bianchini, M., Peguillet, I., Lantz, O.,..., Mordoh, J. (2008) . A phase I clinical study of vaccination of melanoma patients with dendritic cells loaded with allogeneic apoptotic/necrotic melanoma cells. Analysis of toxicity and immune response to the vaccine and of IL-10-1082 promoter genotype as predictor of disease progression. Journal of Translational Medicine, 6.
http://dx.doi.org/10.1186/1479-5876-6-6
---------- CHICAGO ----------
von Euw, E.M., Barrio, M.M., Furman, D., Levy, E.M., Bianchini, M., Peguillet, I., et al. "A phase I clinical study of vaccination of melanoma patients with dendritic cells loaded with allogeneic apoptotic/necrotic melanoma cells. Analysis of toxicity and immune response to the vaccine and of IL-10-1082 promoter genotype as predictor of disease progression" . Journal of Translational Medicine 6 (2008).
http://dx.doi.org/10.1186/1479-5876-6-6
---------- MLA ----------
von Euw, E.M., Barrio, M.M., Furman, D., Levy, E.M., Bianchini, M., Peguillet, I., et al. "A phase I clinical study of vaccination of melanoma patients with dendritic cells loaded with allogeneic apoptotic/necrotic melanoma cells. Analysis of toxicity and immune response to the vaccine and of IL-10-1082 promoter genotype as predictor of disease progression" . Journal of Translational Medicine, vol. 6, 2008.
http://dx.doi.org/10.1186/1479-5876-6-6
---------- VANCOUVER ----------
von Euw, E.M., Barrio, M.M., Furman, D., Levy, E.M., Bianchini, M., Peguillet, I., et al. A phase I clinical study of vaccination of melanoma patients with dendritic cells loaded with allogeneic apoptotic/necrotic melanoma cells. Analysis of toxicity and immune response to the vaccine and of IL-10-1082 promoter genotype as predictor of disease progression. J. Transl. Med. 2008;6.
http://dx.doi.org/10.1186/1479-5876-6-6