Department of Pediatric Oncology, Hematology and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany.
Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
Front Immunol. 2023 Mar 24;14:1110522. doi: 10.3389/fimmu.2023.1110522. eCollection 2023.
Viral-based cancer therapies have tremendous potential, especially in the context of treating poorly infiltrated cold tumors. However, in tumors with intact anti-viral interferon (IFN) pathways, while some oncolytic viruses induce strong innate and adaptive immune responses, they are neutralized before exerting their therapeutic effect. Arenaviruses, particularly the lymphocytic choriomeningitis virus (LCMV) is a noncytopathic virus with preferential cancer tropism and evolutionary mechanisms to escape the immune system for longer and to block early clearance. These escape mechanisms include inhibition of the MAVS dependent IFN pathway and spike protein antigen masking. Regarding its potential for cancer treatment, LCMV is therefore able to elicit long-term responses within the tumor microenvironment (TME), boost anti-tumor immune responses and polarize poorly infiltrating tumors towards a hot phenotype. Other arenaviruses including the attenuated Junin virus vaccine also have anti-tumor effects. Furthermore, the LCMV and Pichinde arenaviruses are currently being used to create vector-based vaccines with attenuated but replicating virus. This review focuses on highlighting the potential of arenaviruses as anti-cancer therapies. This includes providing a molecular understanding of its tropism as well as highlighting past and present preclinical and clinical applications of noncytophatic arenavirus therapies and their potential in bridging the gap in the treatment of cancers weakly responsive or unresponsive to oncolytic viruses. In summary, arenaviruses represent promising new therapies to broaden the arsenal of anti-tumor therapies for generating an immunogenic tumor microenvironment.
病毒为基础的癌症疗法具有巨大的潜力，特别是在治疗浸润不良的冷肿瘤方面。然而，在具有完整抗病毒干扰素（IFN）途径的肿瘤中，虽然一些溶瘤病毒会诱导强烈的先天和适应性免疫反应，但它们在发挥治疗作用之前就被中和了。沙粒病毒，特别是淋巴细胞性脉络丛脑膜炎病毒（LCMV），是一种非细胞病变病毒，具有优先的癌症趋向性和逃避免疫系统的进化机制，以更长时间和阻止早期清除。这些逃避机制包括抑制 MAVS 依赖性 IFN 途径和刺突蛋白抗原掩蔽。关于其在癌症治疗中的潜力，因此，LCMV 能够在肿瘤微环境（TME）内引发长期反应，增强抗肿瘤免疫反应，并使浸润不良的肿瘤向热表型极化。其他沙粒病毒，包括减毒的胡宁病毒疫苗，也具有抗肿瘤作用。此外，LCMV 和皮钦德沙粒病毒目前正被用于制造基于载体的疫苗，这些疫苗具有减弱但复制的病毒。这篇综述重点强调了沙粒病毒作为抗癌疗法的潜力。这包括提供对其趋向性的分子理解，以及强调过去和现在非细胞病变沙粒病毒疗法的临床前和临床应用及其在弥合对溶瘤病毒反应弱或无反应的癌症治疗差距方面的潜力。总之，沙粒病毒代表了有前途的新疗法，可以扩大抗肿瘤疗法的武器库，以产生免疫原性肿瘤微环境。
