Abstract 2210: Multiple antigens stimulating cellular therapy increases immune responses in patients with hepatocellular carcinoma

Abstract

Abstract Background & Aims: Hepatocellular carcinoma (HCC) is one of the most common tumors in China, and frequently occurs in the patients with chronic hepatitis B virus (HBV) infection. To investigate whether adoptive cell therapy induces tumor specific immune responses in HCC patients and further brings clinical benefits, Multiple Antigens Stimulating Cellular Therapy (MASCT) was applied in addition to conventional therapies. Methods: Activated T cells that were prepared from the autologous peripheral blood mononuclear cells (PBMCs). Cells were stimulated and amplified with dendritic cells (DCs) pulsed by multiple tumor antigen peptides, including tumor associated antigen peptides and HBV antigen peptides. All patients received infusions of 5-10×107cells/kg of body weight of the resulting T cells every 1-3 months. The immune responses in the patients' PBMCs were examined before and after the treatment. Results: The resulting amplified cells were almost exclusively CD3+ (95% ± 1%), with a major percentage being CD3+CD8+ cells (70% ± 5%) and a minor proportion being CD3+CD4+(19% ± 3%) and CD3+CD56+ (14% ± 1%) cells, while there were insignificant amounts of CD4+CD25+Foxp3+ regulatory T cells (0.4% ± 0.1%). These T cells have restored immune functions and HLA-restricted specific cytotoxicity against HCC cells. After repeating treatment of MASCT, the frequency of regulatory T cells in the patients’ PBMCs was significantly decreased, and the proliferation and function of tumor antigen specific T cells were enhanced. The specific immune responses against each kind of tumor antigens were also detected in patients. And these immune responses were gradually increased during the treatment of MASCT. Moreover, in retrospective study, the disease control rate (DCR) in one year was found to be raised to 80% in stage B HCC patients receiving MASCT combined with conventional therapies. Conclusions: Our study has demonstrated that MASCT is a well tolerate immunotherapy in patients with HCC. Specific T cell responses against tumor antigens can be strongly induced in vivo. Our study also indicated that repeated MASCT treatment improves both the immunologic function and disease control of patients with HCC. Citation Format: Yanyan Han, Jing Huang, Ran Tao, Yabing Guo, Li Liu, Dongyun Wu, Jin Li, Xiangjun Zhou, Jinlin Hou. Multiple antigens stimulating cellular therapy increases immune responses in patients with hepatocellular carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2210.