Ganesh Shanthi, Gonzalez Edick Melissa, Idamakanti Neeraja, Abramova Marina, Vanroey Melinda, Robinson Michael, Yun Chae-Ok, Jooss Karin
Cell Genesys, Inc., South San Francisco, California 94080, USA.
Cancer Res. 2007 May 1;67(9):4399-407. doi: 10.1158/0008-5472.CAN-06-4260.
Selective replication of oncolytic viruses in tumor cells provides a promising approach for the treatment of human cancers. One of the limitations observed with oncolytic viruses currently used in the treatment of solid tumors is the inefficient spread of virus throughout the tumor mass following intratumoral injection. Data are presented showing that oncolytic adenoviruses expressing the relaxin gene and containing an Ad5/Ad35 chimeric fiber showed significantly enhanced transduction and increased virus spread throughout the tumor when compared with non-relaxin-expressing, Ad5-based viruses. The increased spread of such viruses throughout tumors correlated well with improved antitumor efficacy and overall survival in two highly metastatic tumor models. Furthermore, nonreplicating viruses expressing relaxin did not increase metastases, suggesting that high level expression of relaxin will not enhance metastatic spread of tumors. In summary, the data show that relaxin may play a role in rearranging matrix components within tumors, which helps recombinant oncolytic adenoviruses to spread effectively throughout the tumor mass and thereby increase the extent of viral replication within the tumor. Expressing relaxin from Ad5/Ad35 fiber chimeric adenoviruses may prove a potent and novel approach to treating patients with cancer.
溶瘤病毒在肿瘤细胞中的选择性复制为人类癌症的治疗提供了一种很有前景的方法。目前用于实体瘤治疗的溶瘤病毒存在的局限性之一是瘤内注射后病毒在整个肿瘤块中的传播效率低下。所呈现的数据表明，与不表达松弛素的基于Ad5的病毒相比，表达松弛素基因且含有Ad5/Ad35嵌合纤维的溶瘤腺病毒显示出显著增强的转导作用，并增加了病毒在整个肿瘤中的传播。在两种高转移性肿瘤模型中，此类病毒在肿瘤中的传播增加与抗肿瘤疗效的改善和总体生存期的延长密切相关。此外，表达松弛素的非复制型病毒并未增加转移，这表明松弛素的高水平表达不会增强肿瘤的转移扩散。总之，数据表明松弛素可能在重新排列肿瘤内的基质成分中发挥作用，这有助于重组溶瘤腺病毒在整个肿瘤块中有效传播，从而增加病毒在肿瘤内的复制程度。从Ad5/Ad35纤维嵌合腺病毒表达松弛素可能是一种治疗癌症患者的有效且新颖的方法。
