Targeted delivery of chemotherapeutics: tumor-activated prodrug therapy

被引:184
作者
Chari, RVJ [1 ]
机构
[1] Immunogen Inc, Cambridge, MA 02139 USA
关键词
antibody-drug conjugates; cancer; prodrugs; anti-cancer agents;
D O I
10.1016/S0169-409X(97)00095-1
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The potential of targeted delivery of chemotherapeutic drugs for the treatment of cancer has not yet been realized owing to the difficulty of delivering therapeutic concentrations to the target site. While in vivo studies in animal tumor models have produced very encouraging results, clinical studies with antibody-drug conjugates have been less successful. This paper will review the current status of the targeted delivery approach and analyze some of the reasons for the lack of success so far. Starting with a historical perspective, this review will end with a description of newer, more potent and specific antibody-drug conjugates, which behave like tumor-activated prodrugs that may yet fulfil the promise of the targeted delivery approach for the treatment of cancer. (C) 1998 Elsevier Science B.V.
引用
收藏
页码:89 / 104
页数:16
相关论文
共 65 条
[1]   INHIBITION OF HUMAN-TUMOR GROWTH IN NUDE-MICE BY A CONJUGATE OF DOXORUBICIN WITH MONOCLONAL-ANTIBODIES TO EPIDERMAL GROWTH-FACTOR RECEPTOR [J].
ABOUDPIRAK, E ;
HURWITZ, E ;
BELLOT, F ;
SCHLESSINGER, J ;
SELA, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (10) :3778-3781
[2]  
[Anonymous], IMMUNOCONJUGATES ANT
[3]  
APELGREN LD, 1990, CANCER RES, V50, P3540
[4]  
BAECKSTROM D, 1991, J BIOL CHEM, V266, P21537
[5]   STABILIZATION OF CHIMERIC BR96-DOXORUBICIN IMMUNOCONJUGATE [J].
BARBOUR, NP ;
PABORJI, M ;
ALEXANDER, TC ;
COPPOLA, WP ;
BOGARDUS, JB .
PHARMACEUTICAL RESEARCH, 1995, 12 (02) :215-222
[6]   Phase II study of weekly intravenous recombinant humanized Anti-p185(HER2) monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast [J].
Baselga, J ;
Tripathy, D ;
Mendelsohn, J ;
Baughman, S ;
Benz, CC ;
Dantis, L ;
Sklarin, NT ;
Seidman, AD ;
Hudis, CA ;
Moore, J ;
Rosen, PP ;
Twaddell, T ;
Henderson, IC ;
Norton, L .
JOURNAL OF CLINICAL ONCOLOGY, 1996, 14 (03) :737-744
[7]  
BRASLAWSKY GR, 1990, CANCER RES, V50, P6608
[8]  
CARPENTERG, 1979, ANN REV BIOCH, V48, P194
[9]  
CARROLL AM, 1989, ANTIBODIES RADIODIAG, P13
[10]  
CHARI RVJ, 1995, CANCER RES, V55, P4079