LTX-401 is a novel oncolytic compound designed for the local treatment of solid tumors. In the present study, we have examined the applicability and efficacy of LTX-401 in a rat model JM1 hepatocellular carcinoma, with particular interest in its ability to induce antitumor immunity. LTX-401 induces necrotic cell death followed by the release of immunogenic cell death mediators such as high-mobility group box 1 protein, ATP, and cytochrome c. When injected into subcutaneous and orthotopic JM1 tumors, LTX-401 treatment resulted in a strong antitumoral effect followed by complete tumor regression in the majority of animals. Additionally, LTX-401 could affect the growth of distal tumor deposits simulating metastases, hence indicating immune-mediated abscopal responses. Furthermore, LTX-401 treatment induced tumor-specific immune responses as seen by protection against tumor rechallenge and increased production of interferon-gamma (IFN-γ) by splenic cells in response to stimulation with tumor cells. Taken together, our data demonstrate that the oncolytic compound LTX-401 provides local tumor control followed by protective immune responses and may be exploited as a novel immunotherapeutic agent in hepatocellular carcinoma.

LTX-401是设计用于局部治疗实体瘤的新型溶瘤化合物。在本研究中，我们研究了LTX-401在大鼠JM1肝细胞癌模型中的适用性和功效，特别是其诱导抗肿瘤免疫的能力。LTX-401诱导坏死性细胞死亡，然后释放免疫原性细胞死亡介体，例如高迁移率族box 1蛋白，ATP和细胞色素c。当将LTX-401注射入皮下和原位JM1肿瘤中时，会产生强大的抗肿瘤作用，然后在大多数动物中完全消退肿瘤。此外，LTX-401可能会影响模拟转移的远端肿瘤沉积物的生长，因此表明免疫介导的原始反应。此外，LTX-401疗法可诱导肿瘤特异性免疫反应，如针对肿瘤再发的保护作用以及脾细胞响应肿瘤细胞刺激而产生的干扰素-γ（IFN-γ）产量增加​​所见。两者合计，我们的数据表明溶瘤化合物LTX-401提供局部肿瘤控制，然后进行保护性免疫反应，并可能被用作肝细胞癌的新型免疫治疗剂。