Specifically targeting the CD22 receptor of human B-cell lymphomas with RNA damaging agents: A new generation of therapeutics

被引:32
作者
Hursey, M [1 ]
Newton, DL [1 ]
Hansen, HJ [1 ]
Ruby, D [1 ]
Goldenberg, DM [1 ]
Rybak, SM [1 ]
机构
[1] NCI, Div Canc Treatment & Diag, Dev Therapeut Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA
关键词
antibody; ribonuclease; cancer; immunotoxin; apoptosis; CD22;
D O I
10.1080/10428190290021380
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Targeting CD22 on human B-cells with a monoclonal antibody conjugated to a cytotoxic RNAse causes potent and specific killing of the lymphoma cells in vitro. This translates to anti-tumor effects in human lymphoma models in SCID mice. RNA damage caused by RNAses could be an important alternative to standard DNA-damaging chemotherapeutics. A second generation construct with an improved recombinant cytotoxic RNAse is described. Targeted RNAses may overcome problems of toxicity and immunogenicity associated with plant or bacterial toxin-containing immunoconjugates.
引用
收藏
页码:953 / 959
页数:7
相关论文
共 49 条
[1]   FULL ANTITUMOR ACTION OF RECOMBINANT SEMINAL RIBONUCLEASE DEPENDS ON THE REMOVAL OF ITS N-TERMINAL METHIONINE [J].
ADINOLFI, BS ;
CAFARO, V ;
DALESSIO, G ;
DIDONATO, A .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1995, 213 (02) :525-532
[2]  
ALEKSANDROWICZ J, 1958, LANCET, V2, P420
[3]  
ARDELT W, 1991, J BIOL CHEM, V266, P245
[4]  
Benhattar J, 1996, INT J CANCER, V69, P190, DOI 10.1002/(SICI)1097-0215(19960621)69:3<190::AID-IJC7>3.0.CO
[5]  
2-V
[6]   Role of the N terminus in RNase a homologues: Differences in catalytic activity, ribonuclease inhibitor interaction and cytotoxicity [J].
Boix, E ;
Wu, YN ;
Vasandani, VM ;
Saxena, SK ;
Ardelt, W ;
Ladner, J ;
Youle, RJ .
JOURNAL OF MOLECULAR BIOLOGY, 1996, 257 (05) :992-1007
[7]   Evaluation of immunotoxins containing single-chain ribosome-inactivating proteins and an anti-CD22 monoclonal antibody (OM124):: in vitro and in vivo studies [J].
Bolognesi, A ;
Tazzari, PL ;
Olivieri, F ;
Polito, L ;
Lemoli, R ;
Terenzi, A ;
Pasqualucci, L ;
Falini, B ;
Stirpe, F .
BRITISH JOURNAL OF HAEMATOLOGY, 1998, 101 (01) :179-188
[8]  
CASELLAS P, 1988, IMMUNOTOXINS, P351
[9]   A gender-specific mRNA encoding a cytotoxic ribonuclease contains a 3′ UTR of unusual length and structure [J].
Chen, SL ;
Le, SY ;
Newton, DL ;
Maizel, JV ;
Rybak, SM .
NUCLEIC ACIDS RESEARCH, 2000, 28 (12) :2375-2382
[10]   CYTOSTATIC AND CYTO-TOXIC EFFECTS OF PANNON (P-30 PROTEIN), A NOVEL ANTICANCER AGENT [J].
DARZYNKIEWICZ, Z ;
CARTER, SP ;
MIKULSKI, SM ;
ARDELT, WJ ;
SHOGEN, K .
CELL AND TISSUE KINETICS, 1988, 21 (03) :169-182