Systemic antitumor immunity in experimental brain tumor therapy using a multimutated, replication-competent herpes simplex virus
Systemic antitumor immunity in experimental brain tumor therapy using a multimutated, replication-competent herpes simplex virus
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DOI：
10.1089/10430349950016483
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发表时间：
1999-11-20
影响因子：
4.2
通讯作者：
Martuza, RL
中科院分区：
文献类型：
--
作者：
Todo, T;Rabkin, SD;Martuza, RL
具有复制能力的减毒单纯疱疹病毒（HSV）载体已被开发用于原发性和转移性恶性脑肿瘤的病毒溶瘤治疗。然而，宿主免疫反应在大脑中的作用尚未阐明。 N18 神经母细胞瘤细胞仅用作同基因 A/J 小鼠的肿瘤模型，以测试 G207（一种条件复制 HSV 载体）在免疫活性条件下的治疗效果。肿瘤内接种的 G207 在脑部或皮下携带 N18 肿瘤的小鼠中表现出显着的溶瘤抗肿瘤作用，此外，还引发了全身抗肿瘤免疫反应。G207 的皮下肿瘤治疗导致脑部或外周远处已形成的肿瘤消退，这可能是由全身抗肿瘤免疫反应介导的，并且还提供了针对脑部 N18 肿瘤再攻击的持久肿瘤特异性保护就像在外围一样。抗肿瘤免疫与针对 N18 肿瘤细胞的特异性 CTL 活性升高相关，这种活性持续至少 13 个月。结果表明，具有复制能力的 HSV 的溶瘤抗肿瘤作用可以通过诱导外周和大脑中有效的特异性和全身性抗肿瘤免疫来增强。
Replication-competent, attenuated herpes simplex virus (HSV) vectors have been developed for viral oncolytic therapy of primary and metastatic malignant brain tumors. However, the role of the host immune responses in the brain has not been elucidated. N18 neuroblastoma cells mere used as a tumor model in syngeneic A/J mice to test the therapeutic efficacy of G207, a conditionally replicating HSV vector, in an immunocompetent condition. G207 inoculated intraneoplastically exhibited a prominent oncolytic antitumor effect in mice harboring N18 tumors in the brain or subcutaneously, and, in addition, elicited a systemic antitumor immune response, Subcutaneous tumor therapy with G207 caused regression of a remote, established tumor in the brain or in the periphery, which was potentially mediated hy the systemic antitumor immune response, and provided persistent tumor-specific protection against N18 tumor rechallenge in the brain as well as in the periphery. Antitumor immunity was associated with an elevation of specific CTL activity against N18 tumor cells that persisted for at least 13 months. The results suggest that the oncolytic antitumor action of replication-competent HSV may be augmented by induction of specific and systemic antitumor immunity effective both in the periphery and in the brain.