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

Poster Board Number: A334

Lei Yang (Yale University), Kien Pham (Yale University), Timur Yarovinsky (Yale University), Samuel Defina (Yale University), John Rose (Yale University), Chen Liu (Yale University)

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.

Yale University