Personalized mRNA Vaccine Combined with PD-1 Inhibitor Therapy in a Patient with Advanced Esophageal Squamous Cell Carcinoma

Abstract

Abstract Background Therapeutic cancer vaccines serve as a valuable tool to educate the immune system to fight tumors precisely. Cancer cells have characteristics of genetic instability and rapidly accumulate somatic mutations rapidly, which can result in the production of tumour-specific antigens (TSAs) called neoantigens. The main goal of neoantigen-based cancer vaccines is to activate the immune system and effective tumor-specific T-cell responses against cancer cells. Patients with advanced esophageal squamous cell carcinoma (ESCC) who achieved partial remission after personalized mRNA vaccine treatment have not been reported. As personalized neoantigen-based immunotherapies are emerging, we report a case in which mRNA vaccines were used to treat advanced ESCC firstly.Methods Samples of tissues from the recurrence focus in the esophagus were subjected to whole transcriptome sequencing. The neoantigens were identified by bioinformatics analyses and the top 20 neoantigens were selected. These 20 neoantigens, composing the polyneoantigen vaccine, were administered at 1 mg every 3 weeks for 4 cycles in combination with a PD-1 inhibitor, and 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. The lesions were evaluated by imaging examination.Results Our results revealed that neoantigen-based vaccines significantly activated the tumour-specific immune response. TCR V-J pairing analysis showed that the abundance of oligoclonal TCRs was increased, that is, the homogeneity was improved. No other grade 3 or higher drug-related adverse events were observed, except for grade 4 thrombocytopenia, which was caused by PD-1 inhibitor treatment. The patient reported here achieved a partial response (PR).Conclusions Our report showed that combining the personalized mRNA vaccine therapy with PD-1 blockade therapy may be an effective treatment strategy for this patient with advanced esophageal cancer. However, further study should be performed in clinical trials to confirm the efficacy and safety of personalized neoantigen-based immunotherapies in the treatment of advanced ESCC .