Immunocytokines: amplification of anti-cancer immunity

被引:34
作者
Davis, CB [1 ]
Gillies, SD [1 ]
机构
[1] EMD Lexigen Res Ctr, Billerica, MA 01821 USA
关键词
antibody; cytokine; EpCAM; GD2; immunotherapy; interleukin-2;
D O I
10.1007/s00262-002-0349-4
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Many cancers elicit an anti-tumor immune response, which is nevertheless unable to protect the patient. One approach to boost anti-tumor immunity is to target immunostimulatory cytokines to the tumor. Such targeting can be achieved by generating chimeric proteins (immunocytokines) in which the cytokine in question is fused to the C-terminus of a tumor-specific antibody. Immunocytokines containing interleukin-2 (IL-2) have been efficacious in mouse tumor models and have entered clinical trials. Numerous enhancements of immunocytokines are possible, including use of additional stimulatory cytokines, alternate modes of tumor targeting, structural modifications to improve pharmacokinetics, and removal of potentially immunogenic sequences from the fusion protein. In addition, immunocytokines are likely to be efficacious in combination with other therapies, including some forms of chemotherapy and cancer vaccines.
引用
收藏
页码:297 / 308
页数:12
相关论文
共 127 条
[11]   An antibody-interleukin 2 fusion protein overcomes tumor heterogeneity by induction of a cellular immune response [J].
Becker, JC ;
Varki, N ;
Gillies, SD ;
Furukawa, K ;
Reisfeld, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (15) :7826-7831
[12]   Eradication of human hepatic and pulmonary melanoma metastases in SCID mice by antibody-interleukin 2 fusion proteins [J].
Becker, JC ;
Pancook, JD ;
Gillies, SD ;
Mendelsohn, J ;
Reisfeld, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (07) :2702-2707
[13]   T cell-mediated eradication of murine metastatic melanoma induced by targeted interleukin 2 therapy [J].
Becker, JC ;
Pancook, JD ;
Gillies, SD ;
Furukawa, K ;
Reisfeld, RA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (05) :2361-2366
[14]   Long-lived and transferable tumor immunity in mice after targeted interleukin-2 therapy [J].
Becker, JC ;
Varki, N ;
Gillies, SD ;
Furukawa, K ;
Reisfeld, RA .
JOURNAL OF CLINICAL INVESTIGATION, 1996, 98 (12) :2801-2804
[15]   Cytokines as a link between innate and adaptive antitumor immunity [J].
Belardelli, F ;
Ferrantini, M .
TRENDS IN IMMUNOLOGY, 2002, 23 (04) :201-208
[16]   Enhancement of the antitumor properties of interleukin-2 by its targeted delivery to the tumor blood vessel extracellular matrix [J].
Carnemolla, B ;
Borsi, L ;
Balza, E ;
Castellani, P ;
Meazza, R ;
Berndt, A ;
Ferrini, S ;
Kosmehl, H ;
Neri, D ;
Zardi, L .
BLOOD, 2002, 99 (05) :1659-1665
[17]   Improving the efficacy of antibody-based cancer therapies [J].
Carter, P .
NATURE REVIEWS CANCER, 2001, 1 (02) :118-129
[18]   Natural killer cells, viruses and cancer [J].
Cerwenka, A ;
Lanier, LL .
NATURE REVIEWS IMMUNOLOGY, 2001, 1 (01) :41-49
[19]  
CHAN SH, 1992, J IMMUNOL, V148, P92
[20]  
Christ O, 2001, CLIN CANCER RES, V7, P1385