Bryson J S, Cox D C
Department of Microbiology, Miami University, Oxford, Ohio 45056.
Cancer Immunol Immunother. 1988;26(2):132-8. doi: 10.1007/BF00205606.
We have previously demonstrated the ability of reovirus to function synergistically with chemotherapy in the treatment of murine EL-4 lymphoma. This study characterizes this treatment regimen in the therapy of L1210 leukemia. Animals with an estimated tumor burden of 10(7) cells were treated with 9 mg/kg 1,3-bis(2-chloroethyl)-1-nitrosourea. Reovirus type 3, which had been quantitated either by particles or plaque-forming units (pfu), was administered 48 h after chemotherapy. Complete remission of tumor was observed in 80% of the animals which received either 10(11) particles or 10(9) pfu of reovirus. Cured animals were resistant to challenge with homologous tumor, but were susceptible to challenge with heterologous tumor. Reovirus undergoes limited replication at the tumor site, and virus-specific antibody appears only after disappearance of reovirus-infected cells and virus from the ascites fluid. Reovirus appears to function therapeutically by inducing a tumor-specific cytolytic immune response.
我们之前已经证明了呼肠孤病毒在治疗小鼠EL-4淋巴瘤时与化疗协同作用的能力。本研究对该治疗方案在L1210白血病治疗中的情况进行了表征。估计肿瘤负荷为10⁷个细胞的动物接受了9mg/kg的1,3-双(2-氯乙基)-1-亚硝基脲治疗。化疗48小时后,给予经颗粒或空斑形成单位(pfu)定量的3型呼肠孤病毒。接受10¹¹个颗粒或10⁹个pfu呼肠孤病毒的动物中,80%观察到肿瘤完全缓解。治愈的动物对同源肿瘤攻击具有抗性,但对异源肿瘤攻击敏感。呼肠孤病毒在肿瘤部位进行有限复制,病毒特异性抗体仅在呼肠孤病毒感染细胞和病毒从腹水中消失后才出现。呼肠孤病毒似乎通过诱导肿瘤特异性溶细胞免疫反应发挥治疗作用。