DNA vaccines with single-chain Fv fused to fragment C of tetanus toxin induce protective immunity against lymphoma and myeloma

被引：222

作者：

King, CA ^{[1
]}

Spellerberg, MB ^{[1
]}

Zhu, DL ^{[1
]}

Rice, J ^{[1
]}

Sahota, SS ^{[1
]}

Thompsett, AR ^{[1
]}

Hamblin, TJ ^{[1
]}

Radl, J ^{[1
]}

Stevenson, FK ^{[1
]}

机构：

[1] Southampton Univ Hosp Trust, Tenovus Lab, Mol Immunol Grp, Southampton SO16 6YD, Hants, England

来源：

NATURE MEDICINE | 1998年 / 4卷 / 11期

关键词：

D O I：

10.1038/3266

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Vaccination with idiotypic protein protects against B-cell lymphoma, mainly through anti-idiotypic antibody. For use in patients, DNA vaccines containing single-chain Fv derived from tumor provide a convenient alternative vaccine delivery system. However, single-chain Fv sequence alone induces low anti-idiotypic response and poor protection against lymphoma. Fusion of the gene encoding fragment C of tetanus toxin to single-chain Fv substantially promotes the anti-idiotypic response and induces strong protection against B-cell lymphoma. The same fusion design also induces protective immunity against a surface Ig-negative myeloma. These findings indicate that fusion to a pathogen sequence allows a tumor antigen to engage diverse immune mechanisms that suppress growth. This fusion design has the added advantage of overcoming potential tolerance to tumor that may exist in patients.

引用

页码：1281 / 1286

页数：6

共 22 条

[1] Immune response in mice following immunization with DNA encoding fragment C of tetanus toxin [J].

Anderson, R ;

Gao, XM ;

Papakonstantinopoulou, A ;

Roberts, M ;

Dougan, G .

INFECTION AND IMMUNITY, 1996, 64 (08) :3168-3173

[2] Peripheral T cell tolerance as a tumor escape mechanism: Deletion of CD4(+) T cells specific for a monoclonal immunoglobulin idiotype secreted by a plasmacytoma [J].

Bogen, B .

EUROPEAN JOURNAL OF IMMUNOLOGY, 1996, 26 (11) :2671-2679

[3]

Conry RM, 1996, SEMIN ONCOL, V23, P135

[4]

DAVIS HL, 1995, MOL CELL BIOL HUMAN, P368

[5] IDIOTYPIC VACCINATION AGAINST B-CELL LYMPHOMA LEADS TO DORMANT TUMOR [J].

DYKE, RJ ;

MCBRIDE, H ;

GEORGE, AJT ;

HAMBLIN, TJ ;

STEVENSON, FK .

CELLULAR IMMUNOLOGY, 1991, 132 (01) :70-83

[6]

EISEN HN, 1975, TRANSPLANT P, V7, P209

[7]

George A J, 1989, Int Rev Immunol, V4, P271, DOI 10.3109/08830188909044783

[8] A pilot study of idiotypic vaccination for follicular B-cell lymphoma using a genetic approach [J].

Hawkins, RE ;

Russell, SJ ;

Marcus, R ;

Ashworth, LJ ;

Brissnik, J ;

Zhang, J ;

Winter, G ;

Bleehen, NM ;

Stevenson, F ;

Hamblin, T ;

Oscier, D ;

Zhu, DL ;

King, C ;

Kumar, S ;

Thompsett, A ;

Stevenson, GT .

HUMAN GENE THERAPY, 1997, 8 (10) :1287-1299

[9] Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma - Long-term results of a clinical trial [J].

Hsu, FJ ;

Caspar, CB ;

Czerwinski, D ;

Kwak, LW ;

Liles, TM ;

Syrengelas, A ;

TaidiLaskowski, B ;

Levy, R .

BLOOD, 1997, 89 (09) :3129-3135

[10] Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells [J].

Hsu, FJ ;

Benike, C ;

Fagnoni, F ;

Liles, TM ;

Czerwinski, D ;

Taidi, B ;

Engleman, EG ;

Levy, R .

NATURE MEDICINE, 1996, 2 (01) :52-58

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