Personalized neoantigen vaccine prevents postoperative recurrence in hepatocellular carcinoma patients with vascular invasion

Zhixiong Cai,Liman Qiu,Hengkai Chen,Yang Zhou,Zhenli Li,Yongyi Zeng,Xiaolong Liu,Geng Chen,Fuqun Wei,Yingchao Wang,Xiuqing Dong,Xiaoping Su,Xiaolou Li,Liuping Luo

doi:10.1186/s12943-021-01467-8

Abstract

BackgroundClinically, prophylactic anti-recurrence treatments for hepatocellular carcinoma (HCC) patients after radical surgery are extremely limited. Neoantigen based vaccine can generate robust anti-tumor immune response in several solid tumors but whether it could induce anti-tumor immune response in HCC and serve as a safe and effective prophylactic strategy for preventing postoperative HCC recurrence still remain largely unclear.MethodsPersonalized neoantigen vaccine was designed and immunized for 10 HCC patients with high risk of postoperative recurrence in a prime-boost schedule. The safety and immune response were assessed through adverse events, tissue sequencing, ELISpot, TCR sequencing. The clinical response was evaluated by recurrence-free survival (RFS) and personalized circulating tumor DNA (ctDNA) sequencing.ResultsIn the 10 enrolled patients, no obvious adverse events were observed during neoantigen vaccinations. Until the deadline of clinical trial, 8 of 10 patients were confirmed with clinical relapse by imaging, the other 2 patients remained relapse-free. From receiving first neoantigen vaccination, the median RFS of 10 patients were 7.4 months. Among 7 patients received all planned neoantigen vaccinations, 5 of them demonstrated neoantigen-induced T cell responses and have significantly longer RFS after radical surgery than other 5 patients without responsive neoantigens or only with prime vaccination and propensity scores matching control patients (p = 0.035). Moreover, tracking personalized neoantigen mutations in ctDNA could provide real-time evaluation of clinical response in HCC patients during neoantigen vaccination and follow up.ConclusionPersonalized neoantigen vaccine is proved as a safe, feasible and effective strategy for HCC anti-recurrence, and its progression could be sensitively monitored by corresponding neoantigen mutations in ctDNA, and thus provided solid information for individualized medicine in HCC.Trial registrationThis study was registered at Chinese Clinical Trial Registry; Registration number: ChiCTR1900020990.

Highlights

Hepatocellular carcinoma (HCC) is an increasingly serious global pandemic
Previous clinical studies have shown that some hepatocellular carcinoma (HCC) patients with vascular invasion in portal venous branch can still benefit from surgery treatment [2, 3], and such patients could be recommended for surgery treatment following the guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2019 Edition) and EASL Clinical Practice Guidelines [4, 5]
Study design and patient characteristics In this single-arm prospective clinical study, personalized neoantigen profiling was firstly performed for each newly diagnosed HCC patient with vascular invasion based on whole exome sequencing data and transcriptomic sequencing data of surgically resected tumor tissue and matched peritumor tissue (Fig. 1A)

Summary

Introduction

Hepatocellular carcinoma (HCC) is an increasingly serious global pandemic. Especially in China, where new HCC cases account for 55% of the world’s total cases, approximately 422,100 people die from HCC progression per year [1]. Previous clinical studies have shown that some HCC patients with vascular invasion in portal venous branch can still benefit from surgery treatment [2, 3], and such patients could be recommended for surgery treatment following the guidelines for Diagnosis and Treatment of Primary Liver Cancer in China (2019 Edition) and EASL Clinical Practice Guidelines [4, 5]. These patients still suffer a high risk of recurrence and metastasis after surgery. Neoantigen based vaccine can generate robust anti-tumor immune response in several solid tumors but whether it could induce anti-tumor immune response in HCC and serve as a safe and effective prophylactic strategy for preventing postoperative HCC recurrence still remain largely unclear

Methods

Results

Conclusion