Recently, Professor Kuang Ming's team, from the Center of Hepato-Pancreato-Biliary Surgery of The First Affiliated Hospital at Sun Yat-sen University (FAH-SYSU), has made new progress in the field of precise prevention and treatment of hepatocellular carcinoma (HCC) recurrence. Their related outcomes have been published in Cancer Immunology Research, an important journal of the American Association for Cancer Research (AACR), in the form of a paper titled "Combination Neoantigen-Based Dendritic Cell Vaccination and Adoptive T-Cell Transfer Induces Antitumor Responses Against Recurrence of Hepatocellular Carcinoma". This paper reported the results of the first stage of the ongoing REMEC trial (NCT03067493), which is the first prospective phase II clinical trial of adjuvant combination treatment of neoantigen-loaded DC vaccine and neoantigen-activated T-cell therapy to prevent HCC recurrence around the world. The results showed that the combined immunotherapy based on tumor neoantigen is safe and feasible, and can reduce the recurrence of HCC after radical treatment. The results of this study provide new insight for the prevention and treatment of HCC recurrence.
The recurrence rate of HCC within five years after operation is as high as 70%, but there is no effective method to prevent HCC recurrence. The high recurrence rate of HCC is one of the main obstacles affecting the long-term survival of patients. How to prevent the recurrence of HCC has become a major challenge in the clinical management of HCC. Tumor neoantigens are the abnormal protein produced by gene mutations of tumor cells and could be recognized by immune cells. Since they are expressed exclusively in tumor cells, tumor neoantigens are less prone to induce immune tolerance or trigger autoimmune response. Therefore, tumor neoantigen have been considered as a potential immunotherapy treatment target. DC vaccine based on tumor neoantigen and adoptive T cell therapy have been proved to be effective in many solid tumors, but their role in preventing HCC recurrence remains unclear.
The results showed that 70% of HCC patients responded to combined immunotherapy without serious adverse events. 71.4% of immune responders did not relapse for 2 years after curative treatment, and the disease-free survival (DFS) was significantly longer than that of non-responders. Further studies revealed that HCC patients with high tumor mutation burden (TMB), enrichment of DCs and CD8+T cells, and high expression of T cell inflammation related genes in primary tumors were more likely to benefit from combined immunotherapy. In addition, neoantigen depletion (immunoediting) and the newly generated immunogenic clones were observed in recurrent tumors, suggesting that the recurrence of HCC may be related to immune evasion under treatment pressure.
This study is another important progress of Professor Kuang Ming's team in the field of accurate prevention and treatment of HCC recurrence with the support of the clinical database and biological specimen bank of the Center of Hepato-Pancreato-Biliary Surgery and the close cooperation with the Clinical Research Center of FAH-SYSU. It has proved for the first time the safety and effectiveness of combined immunotherapy based on tumor neoantigen in preventing HCC recurrence, and provided new evidence-based medical evidence for the choice of prevention and treatment strategies for HCC recurrence after surgery.
Link to the paper: https://aacrjournals.org/cancerimmunolres/article-abstract/10/6/728/699035/Combination-Neoantigen-Based-Dendritic-Cell?redirectedFrom=fulltext
