Advanced HCC Patient Benefit From Neoantigen Reactive T Cells Based Immunotherapy: A Case Report

Abstract

Advanced hepatocellular carcinoma (HCC) is a highly lethal disease, mainly due to the late stage at diagnosis and its rapid progression. Although patients with advanced HCC can choose targeted therapy or chemotherapy, overall, the treatment response rate is extremely low and the average survival time is one year more or less. But the application of immunotherapy have led to a paradigm shift in the treatment of HCC,such as TILs (tumor infiltrating lymphocytes),Checkpoint blockade (immune Checkpoint blockade), CAR-T(chimeric antigen receptor T cells) and TCR-T (engineered t-cell receptor T cells). And recent data indicate neoantigens generated when tumors mutate are the main target of tumor-specific TILs, and they are also the main antigens mediating tumor regression in TILs treatment. Moreover, numerous evidences have revealed that radiotherapy lead to massive release of tumor antigens, which may increase the effectiveness of immunotherapy. Based on the above theory, we used neoantigen reactive T cells combined with tomotherapy to treat a patient with advanced HCC (Clinical Trial Study Registration Number: NCT03199807), who reached a long time progress free survival.

Keywords: benefit; hepatocellular carcinoma; immunotherapy; neoantigen reactive T cells; tomotherapy.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Liu, Shao, Dong, Xu, Zou, Chen, Yan, Liu, Li, Liu and Shen.

Figures

Figure 1

(A) alpha fetoprotein (AFP) levels of this patient during the treatment of tomotherapy combined with Neoantigen Reactive T Cells. (B) The lymphocyte levels of this patient during the treatment of tomotherapy combined with Neoantigen Reactive T Cells.

Figure 2

Plain and enhanced MRI of lesions in different parts of patient in different periods. a–f: right anterior lobe of the liver; g–l: porta hepatis; m–o: left outer lobe of the liver. Efficacy evaluation: PD, Disease progression; SD, Stable disease; PR, Partial response; CR, Complete response.

Figure 3

The patient received different treatments at different times. Firstly, tomotherapy combined with Neoantigen Reactive T Cells based immunotherapy(2017-02 to 2017-08, SD). Secondly, PD-1 antibody combined with apatinib(2018-05 to 2018-07, PR). Finally, PD-1 antibody single-drug maintenance treatment (2018-07 until 2020-06, PR in porta hepatis and CR in left outer lobe).