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Toxins  2012 

Comparative Antitumor Effect of Preventive versus Therapeutic Vaccines Employing B16 Melanoma Cells Genetically Modified to Express GM-CSF and B7.2 in a Murine Model

DOI: 10.3390/toxins4111058

Keywords: cancer vaccines, gene therapy, non-viral, GM-CSF, B7.2

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Abstract:

Cancer vaccines have always been a subject of gene therapy research. One of the most successful approaches has been working with genetically modified tumor cells. In this study, we describe our approach to achieving an immune response against a murine melanoma model, employing B16 tumor cells expressing GM-CSF and B7.2. Wild B16 cells were injected in C57BL6 mice to cause the tumor. Irradiated B16 cells transfected with GM-CSF, B7.2, or both, were processed as a preventive and therapeutic vaccination. Tumor volumes were measured and survival curves were obtained. Blood samples were taken from mice, and IgGs of each treatment group were also measured. The regulatory T?cells (Treg) of selected groups were quantified using counts of images taken by confocal microscopy. Results: one hundred percent survival was achieved by preventive vaccination with the group of cells transfected with p2F_GM-CSF. Therapeutic vaccination achieved initial inhibition of tumor growth but did not secure overall survival of the animals. Classical Treg cells did not vary among the different groups in this therapeutic vaccination model.

References

[1]  Kim, S.; Carew, J.F.; Kooby, D.A.; Shields, J.; Entwisle, C.; Patel, S.; Shah, J.P.; Fong, Y. Combination gene therapy using multiple immunomodulatory genes transferred by a defective infectious single-cycle herpes virus in squamous cell cancer. Cancer Gene Ther. 2000, 7, 1279–1285.
[2]  Veelken, H.; Mackensen, A.; Lahn, M.; Kohler, G.; Becker, D.; Franke, B.; Brennscheidt, U.; Kulmburg, P.; Rosenthal, F.M.; Keller, H.; et al. A phase-I clinical study of autologous tumor cells plus interleukin-2-gene-transfected allogeneic fibroblasts as a vaccine in patients with cancer. Int. J. Cancer 1997, 70, 269–277, doi:10.1002/(SICI)1097-0215(19970127)70:3<269::AID-IJC4>3.0.CO;2-V.
[3]  Palmer, K.; Moore, J.; Everard, M.; Harris, J.D.; Rodgers, S.; Rees, R.C.; Murray, A.K.; Mascari, R.; Kirkwood, J.; Riches, P.G.; et al. Gene therapy with autologous, interleukin 2-secreting tumor cells in patients with malignant melanoma. Hum. Gene Ther. 1999, 10, 1261–1268, doi:10.1089/10430349950017941.
[4]  Wittig, B.; Marten, A.; Dorbic, T.; Weineck, S.; Min, H.; Niemitz, S.; Trojaneck, B.; Flieger, D.; Kruopis, S.; Albers, A.; et al. Therapeutic vaccination against metastatic carcinoma by expression-modulated and immunomodified autologous tumor cells: A first clinical phase I/II trial. Hum. Gene Ther. 2001, 12, 267–278, doi:10.1089/10430340150218404.
[5]  Moller, P.; Sun, Y.; Dorbic, T.; Alijagic, S.; Makki, A.; Jurgovsky, K.; Schroff, M.; Henz, B.M.; Wittig, B.; Schadendorf, D. Vaccination with IL-7 gene-modified autologous melanoma cells can enhance the anti-melanoma lytic activity in peripheral blood of patients with a good clinical performance status: A clinical phase I study. Br. J. Cancer 1998, 77, 1907–1916, doi:10.1038/bjc.1998.317.
[6]  Maio, M.; Fonsatti, E.; Lamaj, E.; Altomonte, M.; Cattarossi, I.; Santantonio, C.; Melani, C.; Belli, F.; Arienti, F.; Colombo, M.P.; et al. Vaccination of stage IV patients with allogeneic IL-4- or IL-2-gene-transduced melanoma cells generates functional antibodies against vaccinating and autologous melanoma cells. Cancer Immunol. Immunother. 2002, 51, 9–14, doi:10.1007/s00262-001-0249-z.
[7]  Arienti, F.; Belli, F.; Napolitano, F.; Sule-Suso, J.; Mazzocchi, A.; Gallino, G.F.; Cattelan, A.; Santantonio, C.; Rivoltini, L.; Melani, C.; et al. Vaccination of melanoma patients with interleukin 4 gene-transduced allogeneic melanoma cells. Hum. Gene Ther. 1999, 10, 2907–2916, doi:10.1089/10430349950016320.
[8]  Bowman, L.C.; Grossmann, M.; Rill, D.; Brown, M.; Zhong, W.Y.; Alexander, B.; Leimig, T.; Coustan-Smith, E.; Campana, D.; Jenkins, J.; et al. Interleukin-2 gene-modified allogeneic tumor cells for treatment of relapsed neuroblastoma. Hum. Gene Ther. 1998, 9, 1303–1311, doi:10.1089/hum.1998.9.9-1303.
[9]  Belli, F.; Arienti, F.; Sule-Suso, J.; Clemente, C.; Mascheroni, L.; Cattelan, A.; Santantonio, C.; Gallino, G.F.; Melani, C.; Rao, S.; et al. Active immunization of metastatic melanoma patients with interleukin-2-transduced allogeneic melanoma cells: Evaluation of efficacy and tolerability. Cancer Immunol. Immunother. 1997, 44, 197–203, doi:10.1007/s002620050373.
[10]  Olivares, J.; Kumar, P.; Yu, Y.; Maples, P.B.; Senzer, N.; Bedell, C.; Barve, M.; Tong, A.; Pappen, B.O.; Kuhn, J.; et al. Phase I trial of TGF-β2 antisense GM-CSF gene-modified autologous tumor cell (TAG) vaccine. Clin. Cancer Res. 2011, 1, 183–192.
[11]  Agarwalla, P.; Barnard, Z.; Fecci, P.; Dranoff, G.; Curry, W.T., Jr. Sequential immunotherapy by vaccination with GM-CSF-expressing glioma cells and CTLA-4 blockade effectively treats established murine intracranial tumors. J. Immunother. 2012, 35, 385–389, doi:10.1097/CJI.0b013e3182562d59.
[12]  Jaffee, E.M.; Abrams, R.; Cameron, J.; Donehower, R.; Duerr, M.; Gossett, J.; Greten, T.F.; Grochow, L.; Hruban, R.; Kern, S.; Lillemoe, K.D.; O’Reilly, S.; et al. A phase I clinical trial of lethally irradiated allogeneic pancreatic tumor cells transfected with the GM-CSF gene for the treatment of pancreatic adenocarcinoma. Hum. Gene Ther. 1998, 9, 1951–1971, doi:10.1089/hum.1998.9.13-1951.
[13]  Ojima, T.; Iwahashi, M.; Nakamura, M.; Matsuda, K.; Naka, T.; Nakamori, M.; Ueda, K.; Ishida, K.; Yamaue, H. The boosting effect of co-transduction with cytokine genes on cancer vaccine therapy using genetically modified dendritic cells expressing tumor-associated antigen. Int. J. Oncol. 2006, 289, 47–53.
[14]  Dranoff, G.; Jaffee, E.; Lazenby, A.; Golumbek, P.; Levitsky, H.; Brose, K.; Jackson, V.; Hamada, H.; Pardoll, D.; Mulligan, R.C. Vaccination with irradiated tumor cells engineered to secrete granulocyte—Macrophage colony-stimulating factor (GM-CSF) stimulates potent, specific, and long-lasting antitumor immunity in multiple murine tumor model systems, including malignant melanoma. Proc. Natl. Acad. Sci. USA 1993, 90, 3539–3543.
[15]  Parmiani, G.; Castelli, C.; Pilla, L.; Santinami, M.; Colombo, M.P.; Rivoltini, L. Opposite immune functions of GM-CSF administered as vaccine adjuvant in cancer patients. Ann. Oncol. 2007, 18, 226–232.
[16]  Curiel-Lewandrowski, C.; Mahnke, K.; Labeur, M.; Roters, B.; Schmidt, W.; Granstein, R.D.; Luger, T.A.; Schwarz, T.; Grabbe, S. Transfection of immature murine bone marrow-derived dendritic cells with the granulocyte-macrophage colony-stimulating factor gene potently enhances their in vivo antigen-presenting capacity. J. Immunol. 1999, 163, 174–183.
[17]  Dunussi-Joannopoulos, K.; Dranoff, G.; Weinstein, H.J.; Ferrara, J.L.; Bierer, B.E.; Croop, J.M. Gene immunotherapy in murine acute myeloid leukemia: Granulocyte-macrophage colony-stimulating factor tumor cell vaccines elicit more potent antitumor immunity compared with B7 family and other cytokine vaccines. Blood 1998, 91, 222–230.
[18]  Soiffer, R.; Hodi, F.S.; Haluska, F.; Jung, K.; Gillessen, S.; Singer, S.; Tanabe, K.; Duda, R.; Mentzer, S.; Jaklitsch, M.; et al. Vaccination with irradiated, autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma. J. Clin. Oncol. 2003, 21, 3343–3350.
[19]  Nemunaitis, J.; Sterman, D.; Jablons, D.; Smith, J.W.; Fox, B.; Maples, P.; Hamilton, S.; Borellini, F.; Lin, A.; Morali, S.; et al. Granulocyte-macrophage colony-stimulating factor gene-modified autologous tumor vaccines in non-small-cell lung cancer. J. Natl. Cancer Inst. 2004, 96, 326–331, doi:10.1093/jnci/djh028.
[20]  Salgia, R.; Lynch, T.; Skarin, A.; Lucca, J.; Lynch, C.; Jung, K.; Hodi, F.S.; Jaklitsch, M.; Mentzer, S.; Swanson, S.; et al. Vaccination with irradiated autologous tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor augments antitumor immunity in some patients with metastatic non-small-cell lung carcinoma. J. Clin. Oncol. 2003, 21, 624–630.
[21]  Soiffer, R.; Lynch, T.; Mihm, M.; Jung, K.; Rhuda, C.; Schmollinger, J.C.; Hodi, F.S.; Liebster, L.; Lam, P.; Mentzer, S.; et al. Vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte-macrophage colony-stimulating factor generates potent antitumor immunity in patients with metastatic melanoma. Proc. Natl. Acad. Sci.USA 1998, 95, 13141–13146.
[22]  Small, E.J.; Sacks, N.; Nemunaitis, J.; Urba, W.J.; Dula, E.; Centeno, A.S.; Nelson, W.G.; Ando, D.; Howard, C.; Borellini, F.; et al. Granulocyte macrophage colony-stimulating factor—Secreting allogeneic cellular immunotherapy for hormone-refractory prostate cancer. Clin. Cancer Res. 2007, 13, 3883–3891, doi:10.1158/1078-0432.CCR-06-2937.
[23]  Jaffee, E.M.; Hruban, R.H.; Biedrzycki, B.; Laheru, D.; Schepers, K.; Sauter, P.R.; Goemann, M.; Coleman, J.; Grochow, L.; Donehower, R.C.; et al. Novel allogeneic granulocyte-macrophage colony-stimulating factor—Secreting tumor vaccine for pancreatic cancer: A phase I trial of safety and immune activation. J. Clin. Oncol. 2001, 19, 145–156.
[24]  Borrello, I.; Pardoll, D. GM-CSF-based cellular vaccines: A review of the clinical experience. Cytokine Growth Factor Rev. 2002, 13, 185–193, doi:10.1016/S1359-6101(01)00034-X.
[25]  Moret-Tatay, I.; Diaz, J.; Marco, F.M.; Crespo, A.; Ali?o, S.F. Complete tumor prevention by engineered tumor cell vaccines employing nonviral vectors. Cancer Gene Ther. 2003, 10, 887–897, doi:10.1038/sj.cgt.7700646.
[26]  Moret-Tatay, I.; Sanmartín, I.; Marco, F.M.; Díaz, J.; Ali?o, S.F. Nonviral therapeutic cell vaccine mediates potent antitumor effects. Vaccine 2006, 24, 3937–3945.
[27]  Herrero, M.J.; Botella, R.; Dasí, F.; Algás, R.; Sánchez, M.; Ali?o, S.F. Antigens and cytokine genes in antitumor vaccines: The importance of the temporal delivery sequence in antitumor signals. Ann. N. Y. Acad. Sci. 2006, 1091, 412–424, doi:10.1196/annals.1378.084.
[28]  Zhang, X.; Shi, X.; Li, J.; Hu, Z.; Zhou, D.; Gao, J.; Tan, W. A novel therapeutic vaccine of mouse GM-CSF surface modified MB49 cells against metastatic bladder cancer. J. Urol. 2012, 187, 1071–1079.
[29]  Steinman, R.M. The dendritic cell system and its role in immunogenicity. Annu. Rev. Immunol. 1991, 9, 271–296, doi:10.1146/annurev.iy.09.040191.001415.
[30]  Chong, H.; Todryk, S.; Hutchinson, G.; Hart, I.R.; Vile, R.G. Tumor cell expression of B7 costimulatory molecules and interleukin-12 or granulocyte-macrophage colony-stimulating factor induces a local antitumor response and may generate systemic protective immunity. Gene Ther. 1998, 5, 223–232.
[31]  Kim, K.Y.; Kang, M.A.; Nam, M.J. Enhancement of natural killer cell-mediated cytotoxicity by coexpression of GM-CSF/B70 in hepatoma. Cancer Lett. 2001, 166, 33–40, doi:10.1016/S0304-3835(01)00399-8.
[32]  Mukherjee, S.; Nelson, D.; Loh, S.; van Bruggen, I.; Palmer, L.J.; Leong, C.; Garlepp, M.J.; Robinson, B.W. The immune anti-tumor effects of GM-CSF and B7-1 gene transfection are enhanced by surgical debulking of tumor. Cancer Gene Ther. 2001, 8, 580–588, doi:10.1038/sj.cgt.7700347.
[33]  Parney, I.F.; Farr-Jones, M.A.; Kane, K.; Chang, L.J.; Petruk, K.C. Human autologous in vitro models of glioma immunogene therapy using B7-2, GM-CSF and IL-12. Can. J. Neurol. Sci. 2002, 29, 267–275.
[34]  Parney, I.F.; Chang, L.J.; Farr-Jones, M.A.; Hao, C.; Smylie, M.; Petruk, K.C. Technical hurdles in a pilot clinical trial of combined B7-2 and GM-CSF immunogene therapy for glioblastomas and melanomas. J. Neurooncol. 2006, 78, 71–80, doi:10.1007/s11060-005-9058-0.
[35]  Zajac, P.; Oertli, D.; Marti, W.; Adamina, M.; Bolli, M.; Guller, U.; Noppen, C.; Padovan, E.; Schultz-Thater, E.; Heberer, M.; et al. Phase I/II Clinical trial of a nonreplicative vaccinia virus expressing multiple HLA-A0201-restricted tumor-associated epitopes and costimulatory molecules in metastatic melanoma patients. Hum. Gene Ther. 2003, 14, 1497–1510, doi:10.1089/104303403322495016.
[36]  Pizzoferrato, E. B7-2 expression above a threshold elicits anti-tumor immunity as effective as interleukin-12 and prolongs survival in murine B-cell lymphoma. Int. J. Cancer 2004, 110, 61–69, doi:10.1002/ijc.20085.
[37]  Shi, F.S.; Weber, S.; Gan, J.; Rakhmilevich, A.L.; Mahvi, D.M. Granulocyte-macrophage colony-stimulating factor (GM-CSF) secreted by cDNA-transfected tumor cells induces a more potent antitumor response than exogenous GM-CSF. Cancer Gene Ther. 1999, 6, 81–88.
[38]  Herrero, M.J.; Botella, R.; Algás, R.; Marco, F.; Lledó, S.; Ali?o, S.F. Nonviral Cancer Vaccines: From Free Antigens to Engineered Cells. In New Gene Therapy and Cancer Research; Gustafsson, W.B., Ed.; Nova Publishers: New York, NY, USA, 2008.
[39]  Serafini, P.; Carbley, R.; Noonan, K.A.; Tan, G.; Bronte, V.; Borrello, I. High-dose granulocyte-macrophage colony-stimulating factor-producing vaccines impair the immune response through the recruitment of myeloid suppressor cells. Cancer Res. 2004, 64, 6337–6343, doi:10.1158/0008-5472.CAN-04-0757.
[40]  Rodríguez-Lecompte, J.C.; Kruth, S.; Gyorffy, S.; Wan, Y.H.; Gauldie, J. Cell-based cancer gene therapy: Breaking tolerance or inducing autoimmunity. Anim. Health Res. Rev. 2004, 5, 227–234, doi:10.1079/AHR200473.
[41]  Herrero, M.J.; Botella, R.; Algás, R.; Marco, F.; Ali?o, S.F. Bead-selected antitumor genetic cell vaccines. Clin. Med. Oncol. 2008, 2, 257–265.
[42]  Terando, A.M.; Faries, M.B.; Morton, D.L. Vaccine therapy for melanoma: current status and future directions. Vaccine 2007, 25, B4–B16, doi:10.1016/j.vaccine.2007.06.033.
[43]  Zou, W. Regulatory T cells, tumor immunity and immunotherapy. Nat. Rev. Immunol. 2006, 6, 295–307, doi:10.1038/nri1806.
[44]  De Visser, K.; Eichten, A.; Coussens, L. Paradoxical roles of the immune system during cancer development. Nat. Rev. Cancer 2006, 6, 24–37, doi:10.1038/nrc1782.
[45]  Serafini, P.; Borrello, I.; Bronte, V. Myeloid suppressor cells in cancer: Recruitment, phenotype, properties, and mechanisms of immune suppression. Semin. Cancer Biol. 2006, 16, 53–65, doi:10.1016/j.semcancer.2005.07.005.
[46]  Bossiotis, V.A.; Freeman, G.J.; Gribben, J.G.; Badler, L.M. The role of B7-1/B7-2:CD28/CTLA-4 pathways in the prevention of anergy, induction of productive immunity and down-regulation of the immune response. Immunol. Rev. 1996, 15, 5–26.
[47]  Sperling, A.; Bluestone, J.A. The complexities of T-cell co-stimulation: CD28 and beyond. Immunol. Rev. 1996, 153, 155–182, doi:10.1111/j.1600-065X.1996.tb00924.x.
[48]  Marengere, L.E.M.; Waterhouse, H.W.; Duncan, G.S.; Mittrucker, H.W.; Feng, G.S.; Mak, T.W. Regulation of T cell receptor signalling by tyrosine phosphatase SYP association with CTLA-4. Science 1996, 272, 1170–1173.
[49]  Onizuka, S.; Tawara, I.; Shimizu, J.; Sakaguchi, S.; Fujita, T.; Nakayama, E. Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor α) monoclonal antibody. Cancer Res. 1999, 59, 3128–3133.
[50]  Steitz, J.; Brück, J.; Lenz, J.; Knop, J.; Tüting, T. Depletion of CD4+CD25+ T cells and treatment with tyrosinase-related protein 2-transduced dendritic cells enhance the IFN α-induced CD8+ Tcell dependent immune defense of B16 melanoma. Cancer Res. 2001, 61, 8643–8646.
[51]  Nagai, H.; Horikawa, T.; Hara, I.; Fukunaga, A.; Oniki, S.; Oka, M.; Nishigori, C.; Ichihashi, M. In vivo elimination of CD25+ regulatory T cells leads to tumor rejection of B16F10 melanoma, when combined with IL-12 gene transfer. Exp. Dermatol. 2004, 13, 613–620, doi:10.1111/j.0906-6705.2004.00198.x.
[52]  Rech, A.J.; Vonderheide, R.H. Clinical use of anti-CD25 antibody daclizumab to enhance immune responses to tumor antigen vaccination by targeting regulatory T cells. Ann. N. Y. Acad. Sci. 2009, 1174, 99–106, doi:10.1111/j.1749-6632.2009.04939.x.
[53]  Rech, A.J.; Mick, R.; Martin, S.; Recio, A.; Aqui, N.A.; Powell, D.J., Jr.; Colligon, T.A.; Trosko, J.A.; Leinbach, L.I.; Pletcher, C.H.; et al. CD25 blockade depletes and selectively reprograms regulatory T cells in concert with inmunotherapy in cancer patients. Sci. Transl. Med. 2012, 4, 134ra62, doi:10.1126/scitranslmed.3003330.
[54]  Shimizu, J.; Yamazaki, S.; Takahashi, T.; Ishida, Y.; Sakaguchi, S. Stimulation of CD4+CD25+ regulatory T cells through GITR breaks immunological self-tolerance. Nat. Immunol. 2002, 3, 135–142, doi:10.1038/ni759.
[55]  Leach, D.R.; Krummel, M.F.; Allison, J.P. Enhancement of antitumor immunity by CTLA-4 blockade. Science 1996, 271, 1734–1736.
[56]  Ascierto, P.A.; Marincola, F.M.; Ribas, A. Anti-CTLA4 monoclonal antibodies: The past and the future in clinical application. J. Transl. Med. 2011, 9, 196, doi:10.1186/1479-5876-9-196.
[57]  Attia, P.; Maker, A.V.; Haworth, L.R.; Rogers-Freezer, L.; Rosenberg, S.A. Inability of a fusion protein of IL-2 and diphtheria toxin (Denileukin Diftitox, DAB389IL2-ONTAK) to eliminate regulatory T lymphocytes in patients with melanoma. J. Immunother. 2005, 28, 582–592, doi:10.1097/01.cji.0000175468.19742.10.
[58]  Dannull, J.; Su, Z.; Rizzieri, D.; Yang, B.K.; Coleman, D.; Yancey, D.; Zhang, A.; Dahm, P.; Chao, N.; Gilboa, E.; et al. Enhancement of vaccine-mediated antitumor immnunity in cancer patients after depletion of regulatory T cells. J. Clin. Invest. 2005, 115, 3623–3633, doi:10.1172/JCI25947.
[59]  Sharma, R.K.; Elpek, K.G.; Yolcu, E.S.; Schabowsky, R.H.; Zhao, H.; Bandura-Morgan, L.; Shirwan, H. Costimulation as a platform for the development of vaccines: A peptide-based vaccine containing a novel form of 4-1BB ligand eradicates established tumors. Cancer Res. 2009, 69, 4319–4326.
[60]  Sharma, R.K.; Schabowsky, R.H.; Srivastava, A.K.; Elpek, K.G.; Madireddi, S.; Zhao, H.; Zhong, Z.; Miller, R.W.; Macleod, K.J.; Yolcu, E.S.; et al. 4-1BB ligand as an effective multifunctional immunomodulator and antigen delivery vehicle for the development of therapeutic cancer vaccines. Cancer Res. 2010, 70, 3945–3954.
[61]  Madireddi, S.; Schabowsky, R.H.; Srivastava, A.K.; Sharma, R.K.; Yolcu, E.S.; Shirwan, H. SA-4-1BBL costimulation inhibits conversion of conventional CD4+ T cells into CD4+FoxP3+ T regulatory cells by production of IFN-γ. PLoS One 2012, 7, e42459.
[62]  Murphy, K.A.; Lechner, M.G.; Popescu, F.E.; Bedi, J.; Decker, S.A.; Hu, P.; Erickson, J.R.; O’Sullivan, M.G.; Swier, L.; Salazar, A.M.; et al. An in vivo immunotherapy screen of costimulatory molecules identifies Fc-OX40L as a potent reagent for the treatment of established murine gliomas. Clin. Cancer Res. 2012, 18, 4657–4668.
[63]  Horna, P.; Cuenca, A.; Cheng, F.; Brayer, J.; Wang, H.W.; Borrello, I.; Levitsky, H.; Sotomayor, E.M. In vivo disruption of tolerogenic cross-presentation mechanisms uncovers an effective T-cell activation by Bcell lymphomas leading to antitumor immunity. Blood 2006, 107, 2871–2878, doi:10.1182/blood-2005-07-3014.
[64]  Serafini, P.; Meckel, K.; Kelso, M.; Noonan, K.; Califano, J.; Koch, W.; Dolcetti, L.; Bronte, V.; Borrello, I. Phosphodiesterase-5 inhibition augments endogenous antitumor immunity by reducing myeloid-derived suppressor cell function. J. Exp. Med. 2006, 203, 2691–2702, doi:10.1084/jem.20061104.
[65]  Frey, A.B. Myeloid supresor cells regulate the adaptive immune response to cancer. J. Clin. Invest. 2006, 116, 2587–2590, doi:10.1172/JCI29906.
[66]  Filipazzi, P.; Valenti, R.; Huber, V.; Pilla, L.; Canese, P.; Iero, M.; Castelli, C.; Mariani, L.; Parmiani, G.; Rivoltini, L. Identification of a new subset of myeloid supresor cells in Peripherals blood of melanoma patients with modulation by a GM-CSF-based antitumor vaccine. J. Clin. Oncol. 2007, 25, 2546–2553, doi:10.1200/JCO.2006.08.5829.
[67]  Guillem, V.M.; Ali?o, S.F. Transfection pathways of nonspecific and targeted PEI-polyplexes. Gene Ther. Mol. Biol. 2004, 8, 369–384.
[68]  Bordier, C. Phase separation of integral membrane proteins in Triton X-114 solution. J. Biol. Chem. 1981, 25, 1604–1607.

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