Gene-based vaccines and immunotherapeutics

被引:132
作者
Liu, M [1 ]
Acres, B [1 ]
Balloul, JM [1 ]
Bizouarne, N [1 ]
Paul, S [1 ]
Slos, P [1 ]
Squiban, P [1 ]
机构
[1] Transgene SA, F-67082 Strasbourg, France
关键词
D O I
10.1073/pnas.0404845101
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
DNA vaccines, comprised of plasmid DNA encoding proteins from pathogens, allergens, and tumors, are being evaluated as prophylactic vaccines and therapeutic treatments for infectious diseases, allergies, and cancer; plasmids encoding normal human proteins are likewise being tested as vaccines and treatments for autoimmune diseases. Examples of in vivo prophylaxis and immunotherapy, based on different types of immune responses (humoral and cellular), in a variety of disease models and under evaluation in early phase human clinical trials are presented. Viral vectors continue to show better levels of expression than those achieved by DNA plasmid vectors. We have focused our clinical efforts, at this time, on the use of recombinant viral vectors for both vaccine as well as cytokine gene transfer studies. We currently have four clinical programs in cancer immunotherapy. Two nonspecific immunotherapy programs are underway that apply adenoviral vectors for the transfer of cytokine genes into tumors in situ. An adenovirus-IFNgamma construct (TG1042) is currently being tested in phase II clinical trials in cutaneous lymphoma. A similar construct, adenovirus-IL-2 (TG1024), also injected directly into solid tumors, is currently being tested in patients with solid tumors (about one-half of which are melanoma). Encouraging results are seen in both programs. Two cancer vaccine immunotherapy programs focus on two cancer-associated antigens: human papilloma virus E6 and E7 proteins and the epithelial cancer-associated antigen MUC1. Both are encoded by a highly attenuated vaccinia virus vector [modified vaccinia Ankara (MVA)] and both are coexpressed with IL-2. Encouraging results seen in both of these programs are described.
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页码:14567 / 14571
页数:5
相关论文
共 23 条
[1]  
BARAND DL, 1989, P NATL ACAD SCI USA, V86, P7159
[2]   LOSS OF HLA CLASS-I EXPRESSION IN PROSTATE-CANCER - IMPLICATIONS FOR IMMUNOTHERAPY [J].
BLADES, RA ;
KEATING, PJ ;
MCWILLIAM, LJ ;
GEORGE, NJR ;
STERN, PL .
UROLOGY, 1995, 46 (05) :681-686
[3]   Identification of HLA-A2-restricted T-cell epitopes derived from the MUC1 tumor antigen for broadly applicable vaccine therapies [J].
Brossart, P ;
Heinrich, KS ;
Stuhler, G ;
Behnke, L ;
Reichardt, VL ;
Stevanovic, S ;
Muhm, A ;
Rammensee, HG ;
Kanz, L ;
Brugger, W .
BLOOD, 1999, 93 (12) :4309-4317
[4]   ANTIBODIES TO HUMAN-MILK FAT GLOBULE MOLECULES [J].
BURCHELL, J ;
TAYLORPAPADIMITRIOU, J .
CANCER INVESTIGATION, 1989, 7 (01) :53-61
[5]  
Coley WB, 1906, AM J MED SCI, V131, P375
[6]   Adenovirus-mediated intralesional interferon-γ gene transfer induces tumor regressions in cutaneous lymphomas [J].
Dummer, R ;
Hassel, JC ;
Fellenberg, F ;
Eichmüller, S ;
Maier, T ;
Slos, P ;
Acres, B ;
Bleuzen, P ;
Bataille, V ;
Squiban, P ;
Burg, G ;
Urosevic, M .
BLOOD, 2004, 104 (06) :1631-1638
[7]   IMMUNOLOGICAL ANALYSIS OF MUCIN MOLECULES EXPRESSED BY NORMAL AND MALIGNANT MAMMARY EPITHELIAL-CELLS [J].
GRIFFITHS, AB ;
BURCHELL, J ;
GENDLER, S ;
LEWIS, A ;
BLIGHT, K ;
TILLY, R ;
TAYLORPAPADIMITRIOU, J .
INTERNATIONAL JOURNAL OF CANCER, 1987, 40 (03) :319-327
[8]   USE OF A MURINE MONOCLONAL-ANTIBODY FOR DETECTION OF CIRCULATING PLASMA DF3 ANTIGEN LEVELS IN BREAST-CANCER PATIENTS [J].
HAYES, DF ;
SEKINE, H ;
OHNO, T ;
ABE, M ;
KEEFE, K ;
KUFE, DW .
JOURNAL OF CLINICAL INVESTIGATION, 1985, 75 (05) :1671-1678
[9]   CYTOLYTIC T-CELL CLONES AGAINST AN AUTOLOGOUS HUMAN-MELANOMA - SPECIFICITY STUDY AND DEFINITION OF 3 ANTIGENS BY IMMUNOSELECTION [J].
KNUTH, A ;
WOLFEL, T ;
KLEHMANN, E ;
BOON, T ;
ZUMBUSCHENFELDE, KHM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (08) :2804-2808
[10]  
Lin KY, 1996, CANCER RES, V56, P21