Prevention of immune reactions triggered by first-generation adenoviral vectors by monoclonal antibodies and CTLA4Ig.
Prevention of immune reactions triggered by first-generation adenoviral vectors by monoclonal antibodies and CTLA4Ig.
复制标题
通过单克隆抗体和 CTLA4Ig 预防第一代腺病毒载体引发的免疫反应。
作者：
Benoît Guérette;J. Vilquin;Marc Gingras;Claude Gravel;Kathryn J. Wood;J. P. Tremblay
使用第一代载体的腺病毒介导的基因转移的治疗潜力受到以下事实的严重限制，即在免疫活性动物中仅可实现瞬时表达。转基因表达的丧失可至少部分归因于针对载体和/或转基因编码的决定簇的有害免疫应答的出现。FK 506和环孢菌素A均降低这些免疫应答。然而，这些免疫抑制剂在长期使用期间可能引起许多严重的副作用。已经开发了一种替代策略来克服在用编码β-半乳糖苷酶（β-Gal）表达盒的Δ E1/E3 a腺病毒载体体内转染成年免疫活性小鼠的肌肉后的这些问题。YTS 177（抗CD 4单克隆抗体）以及CTLA 4 Ig（重组蛋白）部分控制免疫应答。它们确实能够减少CD 4+和CD 8+细胞的肌肉浸润，但它们不能抑制体液反应。然而，YTS 191（抗CD 4）、YTS 169（抗CD 8）和TIB 213（抗CD 11 a）的联合给药在阻断细胞和体液免疫反应方面非常有效。这种单克隆抗体的组合允许在1个月内强烈和稳定的转基因表达。这些数据强调了单克隆抗体作为腺病毒介导的基因转移的免疫抑制辅助治疗的潜力。
The therapeutic potential of adenovirus-mediated gene transfer using first-generation vectors is severely limited by the fact that only transient expression is achievable in immunocompetent animals. The loss in transgene expression can be attributed at least in part to the appearance of detrimental immune responses directed toward vector and/or transgene-encoded determinants. FK506 and cyclosporin A both reduced these immune responses. These immunosuppressants, however, may induce many severe side effects during prolonged use. An alternative strategy has been developed to overcome these problems following in vivo transfection of muscles of adult immunocompetent mice with a delta E1/E3a adenoviral vector encoding a beta-galactosidase (beta-Gal) expression cassette. YTS 177 (an anti-CD4 monoclonal antibody) as well as CTLA4Ig, a recombinant protein, partially controlled the immune responses. They were indeed able to reduce the muscle infiltration by CD4+ and CD8+ cells but they failed to repress the humoral response. Co-administration of YTS 191 (an anti-CD4), YTS 169 (an anti-CD8), and TIB 213 (an anti-CD11a) was, however, very efficient in blocking both cellular and humoral immune reactions. This combination of monoclonal antibodies allowed strong and stable transgene expression over 1 month. These data underline the potential of monoclonal antibodies as immunosuppressive adjunct treatment for adenovirus-mediated gene transfer.
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影响因子：
4.2
作者：
LI, QT;KAY, MA;WOO, SLC
通讯作者：
WOO, SLC
E2a 缺陷的重组腺病毒在棉鼠肺中延长转基因表达。
影响因子：
4.2
作者：
Engelhardt,JF;Litzky,L;Wilson,JM
通讯作者：
Wilson,JM
影响因子：
158.5
作者：
MENDELL, JR;KISSEL, JT;BURGHES, AHM
通讯作者：
BURGHES, AHM
影响因子：
4.4
作者：
Cosimi Ab;D. Conti;F. Delmonico;FredericI. Preffer;Wee Sl;R. Rothlein;R. Faanes;R. Colvin
通讯作者：
Cosimi Ab;D. Conti;F. Delmonico;FredericI. Preffer;Wee Sl;R. Rothlein;R. Faanes;R. Colvin
DOI：
10.1073/pnas.91.10.4407
发表时间：
1994-05-10
影响因子：
11.1
作者：
YANG, YP;NUNES, FA;WILSON, JM
通讯作者：
WILSON, JM