A new RNase-based immunoconjugate selectively cytotoxic for ErbB2-overexpressing cells

被引:32
作者
De Lorenzo, C [1 ]
Nigro, A [1 ]
Piccoli, R [1 ]
D'Alessio, G [1 ]
机构
[1] Univ Naples, Dipartimento Chim Biol, I-80134 Naples, Italy
关键词
immunoconjugate; RNase; ErbB2; antitumor; immunotherapy;
D O I
10.1016/S0014-5793(02)02527-9
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
We report a new tumor-directed immunoRNase, a chimeric protein made up of an antibody fragment (single-chain Fv fragment) directed to ErbB2, a cell surface receptor. and a non-toxic, human ribonuclease, which upon cell internalization becomes cytotoxic. The immunoRNase is active as a ribonuclease, specifically binds and selectively kills ErbB2-positive cells. ErbB2 is one of the most specific tumor-associated antigens identified so far. overexpressed on tumor cells of different origin. Its choice as target antigen and that of a non-toxic, human RNase as the killer moiety makes this immunoRNase a new. potentially attractive anticancer agent. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:208 / 212
页数:5
相关论文
共 22 条
[1]  
BARTHOLEYNS J, 1977, INT J PEPT PROT RES, V10, P172
[2]   ACTIVITY STAINING OF NUCLEOLYTIC ENZYMES AFTER SODIUM DODECYL-SULFATE POLYACRYLAMIDE-GEL ELECTROPHORESIS - USE OF AQUEOUS ISOPROPANOL TO REMOVE DETERGENT FROM GELS [J].
BLANK, A ;
SUGIYAMA, RH ;
DEKKER, CA .
ANALYTICAL BIOCHEMISTRY, 1982, 120 (02) :267-275
[3]  
Carter P, 2000, Breast Dis, V11, P103
[4]   P185 HER2/NEU EPITOPE MAPPING WITH MURINE MONOCLONAL-ANTIBODIES [J].
CENTIS, F ;
TAGLIABUE, E ;
UPPUGUNDURI, S ;
PELLEGRINI, R ;
MARTIGNONE, S ;
MASTROIANNI, A ;
MENARD, S ;
COLNAGHI, MI .
HYBRIDOMA, 1992, 11 (03) :267-276
[5]  
D'Alatri L, 1998, ANTICANCER RES, V18, P3369
[6]   Design, characterization and anti-tumour cytotoxicity of a panel of recombinant, mammalian ribonuclease-based immunotoxins [J].
Deonarain, MP ;
Epenetos, AA .
BRITISH JOURNAL OF CANCER, 1998, 77 (04) :537-546
[7]   Letter to the Editor:: 1H and 15N sequential assignment and solution secondary structure of 15N labelled human pancreatic ribonuclease [J].
El-Joubary, A ;
Bruix, M ;
Santoro, J ;
Cafaro, V ;
Scognamiglio, R ;
Di Donato, A ;
D'Alessio, G ;
Kövér, KE ;
Batta, G ;
Szilágyi, L ;
Rico, M .
JOURNAL OF BIOMOLECULAR NMR, 1999, 15 (03) :265-266
[8]   AMPLIFICATION OF A NOVEL V-ERBB-RELATED GENE IN A HUMAN MAMMARY-CARCINOMA [J].
KING, CR ;
KRAUS, MH ;
AARONSON, SA .
SCIENCE, 1985, 229 (4717) :974-976
[9]   The EGF receptor family as targets for cancer therapy [J].
Mendelsohn, J ;
Baselga, J .
ONCOGENE, 2000, 19 (56) :6550-6565
[10]  
NEWTON DL, 1992, J BIOL CHEM, V267, P19572