The Rausing Laboratory, Division of Neurosurgery, Department of Clinical Sciences, Lund University, BMC D10, 221 84, Lund, Sweden.
Medical Radiation Physics, Department of Clinical Sciences, Lund University, Lund, Sweden.
BMC Cancer. 2023 Jan 30;23(1):106. doi: 10.1186/s12885-023-10583-1.
A more effective immune response against glioblastoma is needed in order to achieve better tumor control. Radiotherapy can induce anti-tumor mediated immune reactions, in addition to its dose response effects. The complement system can function as a bridge between innate and adaptive immune responses. Combining radiotherapy and complement activating therapy is theoretically interesting.
Radiotherapy at 8 Gy × 2 was combined with treatment against C1-inhibitor (C1-INH), a potent inhibitor of activation of the classical pathway of the complement system. Anti-C1-INH was delivered as intratumoral injections. Fully immunocompetent Fischer 344 rats with NS1 glioblastoma tumors were treated. Survival was monitored as primary outcome. Models with either intracranial or subcutaneous tumors were evaluated separately.
In the intracranial setting, irradiation could prolong survival, but there was no additional survival gain as a result of anti-C1-INH treatment. In animals with subcutaneous tumors, combined radio-immunotherapy with anti-C1-INH and irradiation at 8 Gy × 2 significantly prolonged survival compared to control animals, whereas irradiation or anti-C1-INH treatment as single therapies did not lead to significantly increased survival compared to control animals.
Anti-C1-INH treatment could improve the efficacy of irradiation delivered at sub-therapeutic doses and delay tumor growth in the subcutaneous tumor microenvironment. In the intracranial setting, the doses of anti-C1-INH were not enough to achieve any survival effect in the present setting.
为了更好地控制肿瘤，需要针对神经胶质瘤产生更有效的免疫反应。放射治疗除了其剂量反应效应外，还可以诱导抗肿瘤介导的免疫反应。补体系统可以作为先天免疫和适应性免疫反应之间的桥梁。放射治疗与补体激活治疗相结合在理论上很有趣。
采用 8 Gy×2 的放射治疗联合 C1 抑制剂（C1-INH）治疗，C1-INH 是补体系统经典途径激活的有效抑制剂。抗 C1-INH 作为肿瘤内注射给药。使用具有 NS1 神经胶质瘤肿瘤的完全免疫功能的 Fischer 344 大鼠进行治疗。将生存作为主要结果进行监测。分别评估颅内和皮下肿瘤模型。
在颅内环境中，照射可以延长生存时间，但由于抗 C1-INH 治疗并没有额外的生存获益。在具有皮下肿瘤的动物中，与对照组相比，抗 C1-INH 和 8 Gy×2 放射免疫联合治疗显著延长了生存时间，而放射治疗或抗 C1-INH 单一治疗与对照组相比并未显著延长生存时间。
抗 C1-INH 治疗可以提高亚治疗剂量照射的疗效，并延迟皮下肿瘤微环境中的肿瘤生长。在颅内环境中，在目前的环境中，抗 C1-INH 的剂量不足以产生任何生存效果。
