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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 3/2006

01-03-2006 | Original Article

Effective induction of anti-melanoma immunity following genetic vaccination with synthetic mRNA coding for the fusion protein EGFP.TRP2

Authors: Julia Steitz, Cedrik M. Britten, Thomas Wölfel, Thomas Tüting

Published in: Cancer Immunology, Immunotherapy | Issue 3/2006

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Abstract

RNA-based genetic immunization represents an alternative novel strategy for antigen-specific cancer vaccines. In the present paper we investigate the use of synthetic messenger RNA in an experimental melanoma model. We show that gene gun-based immunization using synthetic RNA mediates gene expression in the epidermis and effectively induces antigen-specific cellular and humoral immunity in mice in vivo. Importantly, bombardment of the skin with RNA coding for the melanocytic self-antigen TRP2 linked to the immunogenic protein EGFP was associated with protection against experimentally induced B16 melanoma lung metastases and vitiligo-like fur depigmentation. Our results provide a scientific basis for clinical trials using synthetic mRNA encoding melanocytic antigens linked to immunogenic helper proteins for vaccination of patients with melanoma.
Literature
1.
2.
Rosenberg SA (2000) Identification of cancer antigens: impact on development of cancer immunotherapies. Cancer J 6(Suppl 3):200
3.
Wölfel T, Van Pel A, Brichard V, Schneider J, Seliger B, Meyer zum Büschenfelde KH, Boon T (1994) Two tyrosinase nonapeptides recognized on HLA-A2 melanomas by autologous cytolytic T lymphocytes. Eur J Immunol 24:759PubMedCrossRef
4.
Wölfel T, Hauer M, Schneider J, Serrano M, Wolfel C, Klehmann-Hieb E, De Plaen E, Hankeln T, Meyer zum Buschenfelde KH, Beach D (1995) A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma. Science 269:1281PubMedCrossRef
5.
Bloom MB, Perry-Lalley D, Robbins PF, Li Y, el-Gamil M, Rosenberg SA, Yang JC (1997) Identification of tyrosinase-related protein 2 as a tumor rejection antigen for the B16 melanoma. J Exp Med 185:453PubMedCrossRef
6.
Tuting T, Steitz J, Bruck J, Gambotto A, Steinbrink K, Deleo AB, Robbins P, Knop J, Enk AH (1999) Dendritic cell-based genetic immunization in mice with a recombinant adenovirus encoding murine TRP2 induces effective anti-melanoma immunity. J Gene Med 1:400PubMedCrossRef
7.
Bowne WB, Srinivasan R, Wolchok JD, Hawkins WG, Blachere NE, Dyall R, Lewis JJ, Houghton AN (1999) Coupling and uncoupling of tumor immunity and autoimmunity. J Exp Med 190:1717PubMedCrossRef
8.
Steitz J, Bruck J, Steinbrink K, Enk A, Knop J, Tuting T (2000) Genetic immunization of mice with human tyrosinase-related protein 2: implications for the immunotherapy of melanoma. Int J Cancer 86:89PubMedCrossRef
9.
Steitz J, Bruck J, Gambotto A, Knop J, Tuting T (2002) Genetic immunization with a melanocytic self-antigen linked to foreign helper sequences breaks tolerance and induces autoimmunity and tumor immunity. Gene Ther 9:208PubMedCrossRef
10.
Britten CM, Meyer RG, Frankenberg N, Huber C, Wölfel T (2004) The use of clonal mRNA as an antigenic format for the detection of antigen-specific T lymphocytes in IFN-γ ELISPOT assays. J Immunol Methods 287:125PubMedCrossRef
11.
Steitz J, Bruck J, Knop J, Tuting T (2001) Adenovirus-transduced dendritic cells stimulate cellular immunity to melanoma via a CD4(+) T cell-dependent mechanism. Gene Ther 8:1255PubMedCrossRef
12.
Bronte V, Apolloni E, Ronca R, Zamboni P, Overwijk WW, Surman DR, Restifo NP, Zanovello P (2000) Genetic vaccination with and quot;self and quot; tyrosinase-related protein 2 causes melanoma eradication but not vitiligo. Cancer Res 60:253PubMed
13.
Lane C, Leitch J, Tan X, Hadjati J, Bramson JL, Wan Y (2004) Vaccination-induced autoimmune vitiligo is a consequence of secondary trauma to the skin. Cancer Res 64:1509PubMedCrossRef
14.
Schreurs MW, Eggert AA, de Boer AJ, Vissers JL, van HT, Offringa R, Figdor CG, Adema GJ (2000) Dendritic cells break tolerance and induce protective immunity against a melanocyte differentiation antigen in an autologous melanoma model. Cancer Res 60:6995PubMed
15.
Shibagaki N, Udey MC (2002) Dendritic cells transduced with protein antigens induce cytotoxic lymphocytes and elicit antitumor immunity. J Immunol 168:2393PubMed
16.
Wang HY, Fu T, Wang G, Zeng G, Perry-Lalley DM, Yang JC, Restifo NP, Hwu P, Wang RF (2002) Induction of CD4(+) T cell-dependent antitumor immunity by TAT-mediated tumor antigen delivery into dendritic cells. J Clin Invest 109:1463PubMedCrossRef
17.
Shimizu K, Thomas EK, Giedlin M, Mule JJ (2001) Enhancement of tumor lysate-pulsed and peptide-pulsed dendritic cell-based vaccines by the addition of foreign helper protein. Cancer Res 61:2618PubMed
18.
Condon C, Watkins SC, Celluzzi CM, Thompson K, Falo LD Jr (1996) DNA-based immunization by in vivo transfection of dendritic cells. Nat Med 2:1122PubMedCrossRef
19.
Porgador A, Irvine KR, Iwasaki A, Barber BH, Restifo NP, Germain RN (1998) Predominant role for directly transfected dendritic cells in antigen presentation to CD8+ T cells after gene gun immunization. J Exp Med 188:1075PubMedCrossRef
20.
Wolff JA, Malone RW, Williams P, Chong W, Acsadi G, Jani A, Felgner PL (1990) Direct gene transfer into mouse muscle in vivo. Science 247:1465PubMedCrossRef
21.
Qiu P, Ziegelhoffer P, Sun J, Yang NS (1996) Gene gun delivery of mRNA in situ results in efficient transgene expression and genetic immunization. Gene Ther 3:262PubMed
22.
Hoerr I, Obst R, Rammensee HG, Jung G (2000) In vivo application of RNA leads to induction of specific cytotoxic T lymphocytes and antibodies. Eur J Immunol 30:1PubMedCrossRef
23.
Boczkowski D, Nair SK, Snyder D, Gilboa E (1996) Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. J Exp Med 184:465PubMedCrossRef
24.
Ashley DM, Faiola B, Nair S, Hale LP, Bigner DD, Gilboa E (1997) Bone marrow-generated dendritic cells pulsed with tumor extracts or tumor RNA induce antitumor immunity against central nervous system tumors. J Exp Med 186:1177PubMedCrossRef
25.
Zhang W, He L, Yuan Z, Xie Z, Wang J, Hamada H, Cao X (1999) Enhanced therapeutic efficacy of tumor RNA-pulsed dendritic cells after genetic modification with lymphotactin. Hum Gene Ther 10:1151PubMedCrossRef
26.
Nair SK, Heiser A, Boczkowski D, Majumdar A, Naoe M, Lebkowski JS, Vieweg J, Gilboa E (2000) Induction of cytotoxic T cell responses and tumor immunity against unrelated tumors using telomerase reverse transcriptase RNA transfected dendritic cells. Nat Med 6:1011PubMedCrossRef
27.
Granstein RD, Ding W, Ozawa H (2000) Induction of anti-tumor immunity with epidermal cells pulsed with tumor-derived RNA or intradermal administration of RNA. J Invest Dermatol 114:632PubMedCrossRef
28.
Strobel I, Berchtold S, Gotze A, Schulze U, Schuler G, Steinkasserer A (2000) Human dendritic cells transfected with either RNA or DNA encoding influenza matrix protein M1 differ in their ability to stimulate cytotoxic T lymphocytes. Gene Ther 7:2028PubMedCrossRef
29.
Thornburg C, Boczkowski D, Gilboa E, Nair SK (2000) Induction of cytotoxic T lymphocytes with dendritic cells transfected with human papillomavirus E6 and E7 RNA: implications for cervical cancer immunotherapy. J Immunother 23:412PubMedCrossRef
30.
Su Z, Peluso MV, Raffegerst SH, Schendel DJ, Roskrow MA (2002) Antigen presenting cells transfected with LMP2a RNA induce CD4+ LMP2a-specific cytotoxic T lymphocytes, which kill via a Fas-independent mechanism. Leuk Lymphoma 43:1651PubMedCrossRef
31.
Weissman D, Ni H, Scales D, Dude A, Capodici J, McGibney K, Abdool A, Isaacs SN, Cannon G, Kariko K (2000) HIV gag mRNA transfection of dendritic cells (DC) delivers encoded antigen to MHC class I and II molecules, causes DC maturation, and induces a potent human in vitro primary immune response. J Immunol 165:4710PubMed
32.
Nair SK, Boczkowski D, Morse M, Cumming RI, Lyerly HK, Gilboa E (1998) Induction of primary carcinoembryonic antigen (CEA)-specific cytotoxic T lymphocytes in vitro using human dendritic cells transfected with RNA. Nat Biotechnol 16:364PubMedCrossRef
33.
Heiser A, Dahm P, Yancey DR, Maurice MA, Boczkowski D, Nair SK, Gilboa E, Vieweg J (2000) Human dendritic cells transfected with RNA encoding prostate-specific antigen stimulate prostate-specific CTL responses in vitro. J Immunol 164:5508PubMed
34.
Su Z, Vieweg J, Weizer AZ, Dahm P, Yancey D, Turaga V, Higgins J, Boczkowski D, Gilboa E, Dannull J (2002) Enhanced induction of telomerase-specific CD4(+) T cells using dendritic cells transfected with RNA encoding a chimeric gene product. Cancer Res 62:5041PubMed
35.
Zeis M, Siegel S, Wagner A, Schmitz M, Marget M, Kuhl-Burmeister R, Adamzik I, Kabelitz D, Dreger P, Schmitz N, Heiser A (2003) Generation of cytotoxic responses in mice and human individuals against hematological malignancies using survivin-RNA-transfected dendritic cells. J Immunol 170:5391PubMed
36.
Siegel S, Wagner A, Kabelitz D, Marget M, Coggin J Jr, Barsoum A, Rohrer J, Schmitz N, Zeis M (2003) Induction of cytotoxic T-cell responses against the oncofetal antigen-immature laminin receptor for the treatment of hematologic malignancies. Blood 102:4416PubMedCrossRef
37.
Liao X, Li Y, Bonini C, Nair S, Gilboa E, Greenberg PD, Yee C (2004) Transfection of RNA encoding tumor antigens following maturation of dendritic cells leads to prolonged presentation of antigen and the generation of high-affinity tumor-reactive cytotoxic T lymphocytes. Mol Ther 9:757PubMedCrossRef
38.
Boczkowski D, Nair SK, Nam JH, Lyerly HK, Gilboa E (2000) Induction of tumor immunity and cytotoxic T lymphocyte responses using dendritic cells transfected with messenger RNA amplified from tumor cells. Cancer Res 60:1028PubMed
39.
Heiser A, Maurice MA, Yancey DR, Wu NZ, Dahm P, Pruitt SK, Boczkowski D, Nair SK, Ballo MS, Gilboa E, Vieweg J (2001) Induction of polyclonal prostate cancer-specific CTL using dendritic cells transfected with amplified tumor RNA. J Immunol 166:2953PubMed
40.
Milazzo C, Reichardt VL, Muller MR, Grunebach F, Brossart P (2003) Induction of myeloma-specific cytotoxic T cells using dendritic cells transfected with tumor-derived RNA. Blood 101:977PubMedCrossRef
41.
Nencioni A, Muller MR, Grunebach F, Garuti A, Mingari MC, Patrone F, Ballestrero A, Brossart P (2003) Dendritic cells transfected with tumor RNA for the induction of antitumor CTL in colorectal cancer. Cancer Gene Ther 10:209PubMedCrossRef
42.
Muller MR, Tsakou G, Grunebach F, Schmidt SM, Brossart P (2004) Induction of chronic lymphocytic leukemia (CLL)-specific CD4-mediated and CD8-mediated T-cell responses using RNA-transfected dendritic cells. Blood 103:1763PubMedCrossRef
43.
Heiser A, Coleman D, Dannull J, Yancey D, Maurice MA, Lallas CD, Dahm P, Niedzwiecki D, Gilboa E, Vieweg J (2002) Autologous dendritic cells transfected with prostate-specific antigen RNA stimulate CTL responses against metastatic prostate tumors. J Clin Invest 109:409PubMedCrossRef
44.
Su Z, Dannull J, Heiser A, Yancey D, Pruitt S, Madden J, Coleman D, Niedzwiecki D, Gilboa E, Vieweg J (2003) Immunological and linical responses in metastatic renal cancer patients vaccinated with tumor RNA-transfected dendritic cells. Cancer Res 63:2127PubMed
45.
Nair SK, Morse M, Boczkowski D, Cumming RI, Vasovic L, Gilboa E, Lyerly HK (2002) Induction of tumor-specific cytotoxic T lymphocytes in cancer patients by autologous tumor RNA-transfected dendritic cells. Ann Surg 235:540PubMedCrossRef
46.
Kobayashi T, Yamanaka R, Homma J, Tsuchiya N, Yajima N, Yoshida S, Tanaka R (2003) Tumor mRNA-loaded dendritic cells elicit tumor-specific CD8(+) cytotoxic T cells in patients with malignant glioma. Cancer Immunol Immunother 52:632PubMedCrossRef
47.
Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K, Akira S (2000) A Toll-like receptor recognizes bacterial DNA. Nature 408:740PubMedCrossRef
48.
Heil F, Hemmi H, Hochrein H, Ampenberger F, Kirschning C, Akira S, Lipford G, Wagner H, Bauer S (2004) Species-specific recognition of single-stranded RNA via toll-like receptor 7 and 8. Science 303:1526PubMedCrossRef
49.
Diebold SS, Kaisho T, Hemmi H, Akira S, Reis e Sousa (2004) Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 303:1529PubMedCrossRef
50.
Steitz J, Bruck J, Lenz J, Buchs S, Tuting T (2005) Peripheral CD8+ T cell tolerance against melanocytic in the skin is regulated in two steps by CD4+ T cells and local inflammation: implications for the pathophysiology of vitiligo. J Invest Dermatol 124:144–155PubMedCrossRef
Metadata
Title
Effective induction of anti-melanoma immunity following genetic vaccination with synthetic mRNA coding for the fusion protein EGFP.TRP2
Authors
Julia Steitz
Cedrik M. Britten
Thomas Wölfel
Thomas Tüting
Publication date
01-03-2006
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 3/2006
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-005-0042-5

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