Virus‐Like Vesicles (VLVs) as Therapeutic Vaccine Vectors for Hepatocellular Carcinoma

Hepatocellular Carcinoma (HCC) is the most common form of liver cancer and is the leading cause of cancer-related mortality globally. Despite the substantial progress that has been made in current treatments, HCC remains malignancy with a high recurrence rate due to a poor prognosis. Therefore, developing novel immunotherapy approaches to treat HCC is crucial to solving this global public health problem. Anti-tumor vaccines are promising strategies to elicit immune responses for anti-tumor immunity. In this study, we designed and cloned an alphavirus-vesiculovirus hybrid vaccine vector VLV-GPC3 that can generate virus-like vesicles (VLVs) as self-amplifying RNA replicons to additionally express GPC3, a cell-surface heparan sulfate proteoglycan is highly expressed in HCC. The potency of the VLV-GPC3 as tumor vaccine was assessed in vivo by immunization of C57BL/6 mice with 108 PFU of VLV-GPC3, followed by subcutaneous implantation of Hepa1-6 HCC cell line cells into C57BL/6 mice. The results showed that VLV-GPC3 immunization could elicit robust GPC3-specific antibody responses and effective protection by increasing CD8+ T cells and minimizing the tumor size. Further, the immunized mouse splenocytes co-cultured with GPC3 could significantly promote IFN-r production and CD4+ T cell proliferation. Our data indicate that VLV-GPC3 could be developed as a novel vaccine candidate and offer a new treatment strategy against HCC.