CELL INTELLIGENCE · 肿瘤细胞治疗研究

Therapeutic cancer vaccines are valuable tools for educating the immune system to fight tumors precisely. Cancer cells are characterized with genetic instability and abundant somatic mutations, leading to the production of tumor specific antigens (TSA) called neoantigens. The main goal of neoantigen-based cancer vaccines is to activate the immune system and elicit effective tumor-specific T-cell responses. There have been no reports of advanced esophageal squamous cell carcinoma (ESCC) cases achieving partial remission after personalized mRNA (messenger RNA) vaccine treatment. As personalized neoantigen-based immunotherapies are emerging, here we report a 67-year-old male patient diagnosed with ESCC and multiple enlarged mediastinal lymph nodes, where mRNA vaccines were used for the first time. Tissue samples from the recurrence focus in the esophagus were subjected to whole transcriptome sequencing. The neoantigens were identified by bioinformatics analyses. The top 20 neoantigens were selected to compose the polyneoantigen vaccine, which were administered at 1 mg every 3 weeks for 4 cycles in combination with a PD-1 (programmed death-1) inhibitor. The patient was boosted with a single dose of the PD-1 inhibitor 8 weeks after the 4th cycle. In addition, immune responses were evaluated before and after the 4 cycles of vaccine therapy, and the lesions were evaluated by imaging examination. Our results revealed that neoantigen-based vaccines significantly activated the tumour-specific immune response. TCR (T cell receptor) V-J pairing analysis showed an increase in the abundance of oligoclonal TCRs, indicating improved homogeneity. No grade 3 or higher drug-related adverse events were observed, except for grade 4 thrombocytopenia caused by PD-1 inhibitor treatment. The patient achieved a partial response (PR), with a progression-free survival (PFS) time of 457 days, the OS (overall survival) time of 457 days, and DOR (duration of response) of 377 days. Our report suggests that combining the personalized mRNA vaccine therapy with PD-1 blockade therapy may be an effective treatment strategy for patient with advanced esophageal cancer. However, further clinical trials are necessary to confirm the efficacy and safety of personalized neoantigen-based immunotherapies in the treatment of advanced ESCC. This trial is registered with ClinicalTrials.gov, NCT03468244 on March 16, 2018, and is now complete.