Therapeutic efficacy of IL-2-loaded hydrogels in a mouse tumor model

被引:29
作者
De Groot, CJ
Cadée, JA
Koten, JW
Hennink, WE
Den Otter, W
机构
[1] Univ Utrecht, Fac Vet Med, Dept Cell Biol & Histol, NL-3508 TD Utrecht, Netherlands
[2] Univ Utrecht, Fac Pharm, Dept Pharmaceut, NL-3508 TD Utrecht, Netherlands
关键词
hydrogel; microspheres; interleukin-2; immunotherapy of cancer;
D O I
10.1002/ijc.10167
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Interleukin-2 (IL-2) is a highly effective anticancer drug if it is applied locally for 5 consecutive days. In most cases this requires S invasive treatments, which is not usually acceptable for either the patient or the clinician. For this reason we have developed dextran-based hydrogels from which the required amount of encapsulated IL-2 (1-4 X 10(6) IU of IL-2) is gradually released during 5-10 days. Initially IL-2-containing macroscopic cylinder-shaped gels (implants), and later IL-2-containing injectable microspheres, were developed. These preparations were characterized in vitro, and the therapeutic activity was tested in DBA/2 mice with SL2 lymphosarcoma. The therapy was given to mice with a large and extensively metastasized tumor load (at least 5% of the body weight). If 1-4 x 106 IU of IL-2 was slowly released from the hydrogels over a period of 5-10 days, the therapeutic effects were very good and comparable to the effects of free IL-2 injections for 5 consecutive days. In conclusion, dextran-based hydrogels are promising systems for the controlled release of IL-2. (C) 2002 Wiley-Liss, Inc.
引用
收藏
页码:134 / 140
页数:7
相关论文
共 40 条
[1]  
ATKINS TW, 1994, J BIOMAT SCI-POLYM E, V6, P651
[2]   Interleukin 2 (IL-2) therapy: potential advantages of locoregional versus systemic administration [J].
Bernsen, MR ;
Tang, JW ;
Everse, LA ;
Koten, JW ;
Den Otter, W .
CANCER TREATMENT REVIEWS, 1999, 25 (02) :73-82
[3]  
Cadée JA, 2000, J BIOMED MATER RES, V50, P397
[4]  
Cadée JA, 2001, J BIOMED MATER RES, V56, P600, DOI 10.1002/1097-4636(20010915)56:4<600::AID-JBM1133>3.0.CO
[5]  
2-I
[6]  
CADEE JA, IN PRESS J CONTROL R
[7]  
Cleland J L, 1997, Pharm Biotechnol, V10, P1
[8]  
COHEN PJ, 1987, AM J PATHOL, V129, P208
[9]   In vitro biocompatibility of biodegradable dextran-based hydrogels tested with human fibroblasts [J].
De Groot, CJ ;
Van Luyn, MJA ;
Van Dijk-Wolthuis, WNE ;
Cadée, JA ;
Plantinga, JA ;
Den Otter, W ;
Hennink, WE .
BIOMATERIALS, 2001, 22 (11) :1197-1203
[10]  
Den Otter W, 1999, HEPATO-GASTROENTEROL, V46, P1280