• 1
    Guilhot F, Roy L, Guilhot J, et al. Interferon therapy in chronic myelogenous leukemia. Hematol Oncol Clin North Am. 2004; 18: 585603.
  • 2
    Pyrhonen SO. Systemic therapy in metastatic renal cell carcinoma. Scand J Surg. 2004; 93: 15661.
  • 3
    Nemunaitis J. GVAX (GMCSF gene modified tumor vaccine) in advanced stage non small cell lung cancer. J Control Release. 2003; 91: 22531.
  • 4
    Portielje JE, Gratama JW, van Ojik HH, et al. IL-12: a promising adjuvant for cancer vaccination. Cancer Immunol Immunother. 2003; 52: 13344.
  • 5
    Sasiain MC, de la Barrera S, Fink S, et al. Interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) are necessary in the early stages of induction of CD4 and CD8 cytotoxic T cells by Mycobacterium leprae heat shock protein (hsp) 65 kD. Clin Exp Immunol. 1998; 114: 196203.
  • 6
    Portielje JE, Lamers CH, Kruit WH, et al. Repeated administrations of interleukin (IL)-12 are associated with persistently elevated plasma levels of IL-10 and declining IFN-gamma, tumor necrosis factor-alpha, IL-6, and IL-8 responses. Clin Cancer Res. 2003; 9: 7683.
  • 7
    Sacco S, Heremans H, Echtenacher B, et al. Protective effect of a single interleukin-12 (IL-12) predose against the toxicity of subsequent chronic IL-12 in mice: role of cytokines and glucocorticoids. Blood. 1997; 90: 44739.
  • 8
    Leonard JP, Sherman ML, Fisher GL, et al. Effects of single-dose interleukin-12 exposure on interleukin-12-associated toxicity and interferon-gamma production. Blood. 1997; 90: 25418.
  • 9
    Masztalerz A, Van Rooijen N, Den Otter W, et al. Mechanisms of macrophage cytotoxicity in IL-2 and IL-12 mediated tumour regression. Cancer Immunol Immunother. 2003; 52: 23542.
  • 10
    Zagozdzon R, Golab J, Stoklosa T, et al. Effective chemo-immunotherapy of L1210 leukemia in vivo using interleukin-12 combined with doxorubicin but not with cyclophosphamide, paclitaxel or cisplatin. Int J Cancer. 1998; 77: 7207.
  • 11
    Tatsumi T, Takehara T, Kanto T, et al. Administration of interleukin-12 enhances the therapeutic efficacy of dendritic cell-based tumor vaccines in mouse hepatocellular carcinoma. Cancer Res. 2001; 61: 75637.
  • 12
    Nastala CL, Edington HD, McKinney TG, et al. Recombinant IL-12 administration induces tumor regression in association with IFN-gamma production. J Immunol. 1994; 153: 1697706.
  • 13
    Dunussi-Joannopoulos K, Runyon K, Erickson J, et al. Vaccines with interleukin-12-transduced acute myeloid leukemia cells elicit very potent therapeutic and long-lasting protective immunity. Blood. 1999; 94: 426373.
  • 14
    Atkins MB, Robertson MJ, Gordon M, et al. Phase I evaluation of intravenous recombinant human interleukin 12 in patients with advanced malignancies. Clin Cancer Res. 1997; 3: 40917.
  • 15
    Lenzi R, Rosenblum M, Verschraegen C, et al. Phase I study of intraperitoneal recombinant human interleukin 12 in patients with Mullerian carcinoma, gastrointestinal primary malignancies, and mesothelioma. Clin Cancer Res. 2002; 8: 368695.
  • 16
    Motzer RJ, Rakhit A, Thompson JA, et al. Randomized multicenter phase II trial of subcutaneous recombinant human interleukin-12 versus interferon-alpha 2a for patients with advanced renal cell carcinoma. J Interferon Cytokine Res. 2001; 21: 25763.
  • 17
    Gollob JA, Mier JW, Veenstra K, et al. Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: ability to maintain IFN-gamma induction is associated with clinical response. Clin Cancer Res. 2000; 6: 167892.
  • 18
    Coughlin CM, Wysocka M, Trinchieri G, et al. The effect of interleukin 12 desensitization on the antitumor efficacy of recombinant interleukin 12. Cancer Res. 1997; 57: 24607.
  • 19
    Asselin-Paturel C, Megherat S, Vergnon I, et al. Differential effect of high doses versus low doses of interleukin-12 on the adoptive transfer of human specific cytotoxic T lymphocyte in autologous lung tumors engrafted into severe combined immunodeficiency disease-nonobese diabetic mice: relation with interleukin-10 induction. Cancer. 2001; 91: 11322.
  • 20
    Cebon J, Jager E, Shackleton MJ, et al. Two phase I studies of low dose recombinant human IL-12 with Melan-A and influenza peptides in subjects with advanced malignant melanoma. Cancer Immunol. 2003; 3: 724.
  • 21
    Tahara H, Zeh HJ, 3rd, Storkus WJ, et al. Fibroblasts genetically engineered to secrete interleukin 12 can suppress tumor growth and induce antitumor immunity to a murine melanoma in vivo. Cancer Res. 1994; 54: 1829.
  • 22
    Tahara H, Zitvogel L, Storkus WJ, et al. Effective eradication of established murine tumors with IL-12 gene therapy using a polycistronic retroviral vector. J Immunol. 1995; 154: 646674.
  • 23
    Zitvogel L, Tahara H, Robbins PD, et al. Cancer immunotherapy of established tumors with IL-12. Effective delivery by genetically engineered fibroblasts. J Immunol. 1995; 155: 1393403.
  • 24
    Gambotto A, Tuting T, McVey DL, et al. Induction of antitumor immunity by direct intratumoral injection of a recombinant adenovirus vector expressing interleukin-12. Cancer Gene Ther. 1999; 6: 4553.
  • 25
    Kang WK, Park C, Yoon HL, et al. Interleukin 12 gene therapy of cancer by peritumoral injection of transduced autologous fibroblasts: outcome of a phase I study. Human Gene Ther. 2001; 12: 67184.
  • 26
    Saudemont A, Buffenoir G, Denys A, et al. Gene transfer of CD154 and IL12 cDNA induces an anti-leukemic immunity in a murine model of acute leukemia. Leukemia. 2002; 16: 163744.
  • 27
    Mazzolini G, Alfaro C, Sangro B, et al. Intratumoral injection of dendritic cells engineered to secrete interleukin-12 by recombinant adenovirus in patients with metastatic gastrointestinal carcinomas. J Clin Oncol. 2005; 23: 9991010.
  • 28
    Barker SE, Grosse SM, Siapati EK, et al. Immunotherapy for neuroblastoma using syngeneic fibroblasts transfected with IL-2 and IL-12. British J Cancer. 2007; 97: 2107.
  • 29
    Tatsumi T, Takehara T, Yamaguchi S, et al. Injection of IL-12 gene-transduced dendritic cells into mouse liver tumor lesions activates both innate and acquired immunity. Gene Ther. 2007; 14: 86371.
  • 30
    Dohnal AM, Graffi S, Witt V, et al. Comparative evaluation of techniques for the manufacturing of dendritic cell-based cancer vaccines. J Cell Mol Med. 2009; 13: 12535.
  • 31
    Dohnal AM, Witt V, Hugel H, et al. Phase I study of tumor Ag-loaded IL-12 secreting semi-mature DC for the treatment of pediatric cancer. Cytotherapy. 2007; 9: 75570.
  • 32
    Labbe A, Tran AH, Paige CJ. Murine model of immune-mediated rejection of the acute lymphoblastic leukemia 70Z/3. J Immunol. 2006; 176: 535461.
  • 33
    Paige CJ, Kincade PW, Ralph P. Murine B cell leukemia line with inducible surface immunoglobulin expression. J Immunol. 1978; 121: 6417.
  • 34
    Yoshimitsu M, Sato T, Tao K, et al. Bioluminescent imaging of a marking transgene and correction of Fabry mice by neonatal injection of recombinant lentiviral vectors. Proc Natl Acad Sci USA. 2004; 101: 1690914.
  • 35
    Dull T, Zufferey R, Kelly M, et al. A third-generation lentivirus vector with a conditional packaging system. J Virol. 1998; 72: 846371.
  • 36
    Silvertown JD, Walia JS, Summerlee AJ, et al. Functional expression of mouse relaxin and mouse relaxin-3 in the lung from an Ebola virus glycoprotein-pseudotyped lentivirus via tracheal delivery. Endocrinology. 2006; 147: 3797808.
  • 37
    Wilson SD, McCay JA, Butterworth LF, et al. Correlation of suppressed natural killer cell activity with altered host resistance models in B6C3F1 mice. Toxicol Appl Pharmacol. 2001; 177: 20818.
  • 38
    Alli RS, Khar A. Interleukin-12 secreted by mature dendritic cells mediates activation of NK cell function. FEBS Lett. 2004; 559: 716.
  • 39
    Redlinger RE Jr, Shimizu T, Remy T, et al. Cellular mechanisms of interleukin-12-mediated neuroblastoma regression. J Pediatr Surg. 2003; 38: 199204.
  • 40
    Alatrash G, Hutson TE, Molto L, et al. Clinical and immunologic effects of subcutaneously administered interleukin-12 and interferon alfa-2b: phase I trial of patients with metastatic renal cell carcinoma or malignant melanoma. J Clin Oncol. 2004; 22: 2891900.
  • 41
    Blachere NE, Morris HK, Braun D, et al. IL-2 is required for the activation of memory CD8+ T cells via antigen cross-presentation. J Immunol. 2006; 176: 7288300.
  • 42
    Coughlin CM, Salhany KE, Wysocka M, et al. Interleukin-12 and interleukin-18 synergistically induce murine tumor regression which involves inhibition of angiogenesis. J Clin Invest. 1998; 101: 144152.
  • 43
    Robertson MJ, Mier JW, Logan T, et al. Clinical and biological effects of recombinant human interleukin-18 administered by intravenous infusion to patients with advanced cancer. Clin Cancer Res. 2006; 12: 426573.
  • 44
    Zobywalski A, Javorovic M, Frankenberger B, et al. Generation of clinical grade dendritic cells with capacity to produce biologically active IL-12p70. J Translational Med. 2007; 5: 1833.
  • 45
    Reis e Sousa C. Dendritic cells in a mature age. Nat Rev Immunol. 2006; 6: 47683.
  • 46
    Zajac AJ, Quinn DG, Cohen PL, et al. Fas-dependent CD4+ cytotoxic T-cell-mediated pathogenesis during virus infection. Proc Natl Acad Sci USA. 1996; 93: 147305.
  • 47
    Hegde NR, Dunn C, Lewinsohn DM, et al. Endogenous human cytomegalovirus gB is presented efficiently by MHC class II molecules to CD4+ CTL. J Experiment. Med. 2005; 202: 110919.
  • 48
    Cooper D, Pride MW, Guo M, et al. Interleukin-12 redirects murine immune responses to soluble or aluminum phosphate adsorbed HSV-2 glycoprotein D towards Th1 and CD4+ CTL responses. Vaccine. 2004; 23: 23646.
  • 49
    Matsushita M, Yamazaki R, Ikeda H, et al. Possible involvement of allogeneic antigens recognised by donor-derived CD4 cytotoxic T cells in selective GVL effects after stem cell transplantation of patients with haematological malignancy. Br J Haematol. 2006; 132: 5665.
  • 50
    Corthay A, Skovseth DK, Lundin KU, et al. Primary antitumor immune response mediated by CD4+ T cells. Immunity. 2005; 22: 37183.
  • 51
    Hombach A, Kohler H, Rappl G, et al. Human CD4+ T cells lyse target cells via granzyme/perforin upon circumvention of MHC class II restriction by an antibody-like immunoreceptor. J Immunol. 2006; 177: 566875.
  • 52
    Zhang Y, Wakita D, Chamoto K, et al. Th1 cell adjuvant therapy combined with tumor vaccination: a novel strategy for promoting CTL responses while avoiding the accumulation of Tregs. Int Immunol. 2007; 19: 15161.
  • 53
    Perez-Diez A, Joncker NT, Choi K, et al. CD4 cells can be more efficient at tumor rejection than CD8 cells. Blood. 2007; 109: 534654.
  • 54
    Chung Y, Qin H, Kang CY, et al. An NKT-mediated autologues vaccine generates CD4 T-cell dependent potent antilymphoma immunity. Blood. 2007; 110: 20139.