BMJ Open 2022;12:e055742. doi:10.1136/bmjopen-2021-055742Open access immunotherapy will be included in the clinical outcome and safety assessment. GraphPad Prism V.8 will be used to plot the ctDNA dynamic curves and immune response curves. Patient and public involvement Patients and the public will understand the design and benefits of our trial through consulting with patient advi- sors and reviewing recruitment information. The patients do not participate in the design of the experiment. The results of the experiment will be kept confidential to the patients. Ethics The procedures set out in this trial protocol are designed to ensure that all persons involved in the trial abide by the ICH harmonised tripartite guideline on Good Clinical Practice (ICH- GCP) and the ethical principles described in the applicable version of the Declaration of Helsinki. The trial will be carried out in keeping with local legal and regulatory requirements. The regulations of the GCP regulations will be respected. Before the start of the trial, all documents have been submitted to the independent ethics committee. The study protocol has been approved by local ethics committee on 21 November 2019 (Protocol version 1.2 (27 September 2019)). Data quality assurance The histological diagnosis will be verified by one of the experienced pathologists. Tumour grading and evalua- tion of post- treatment curative effect should be decided by public consultation with experienced clinicians and radiologists.To ensure the quality of the data, we will follow the stan- dard operating procedures of the Clinical Trial Quality Management Practice Guidelines (CPMP/ICH/135/95) throughout the trial. During the clinical trial process, the supervisor will send the case report form (CRF) to the data management unit in real time, and two data admin- istrators will perform independent double entry and double check. Inconsistent results will be checked and corrected item by item according to CRF. Trial status The trial started in September 2019 and is currently recruiting. The length of clinical phase is about 60 months. (The planned end of the study is the end of 2024). The first patient was treated in August 2020. DISCUSSION Tumour neoantigens are derived from somatic cell muta- tions, which are present in various tumours, and there is a strong heterogeneity among them.32 Cancer neoantigen therapy was first reported in 1979, and this study showed that successfully treated lymphoma patients responded less well to tumour neoantigen therapy.33 Further studies also suggest that patients with low mutation burden may be limited in their use of neoantigen therapy due to the restricted number of immunogenic epitopes.34 In view of this, our study included patients with a high mutation load. Current studies suggest that T- cell- based immune responses are involved in the process of tumour neoan- tigen immunotherapy.10 28 35 36 The most striking feature of T cells is their memorability, which reflects the Table 1 Intervention and assessment schedule for the INP trial Execute projectW- 4–W0 W1 W2 W3 W4 W5 W6 W8 W10 W12 W20 W24 W36 W48 Screening period Sequencing/neoantigen preparation√ Neoantigen immunisation √√ √ √ √ √ √ Physical examination √ √ √ √ √ √ √ √ √ √ √ √ √ √ Laboratory examination √* √ √ √ √ √ √ √ CT/MRI √* √ √ √ √ √ ctDNA detection √* √ √ √ √ √ √ IFN-γ, CD4 +T cells, CD8 +T cells√* √ √ √ AEs (CTCAE) √* √ √ √ √ √ √ √ √ √ √ √ √ √ QLQ (EORTC QLQ- C30) √* √ √ √ √ √ Survival follow- up √ √ √ √ √ √ √ √ √ √ √ √ √ √√ Twice a week. *Need to screen out qualified neoantigens before relevant testing. AE, adverse event; CTCAE, Common Terminology Criteria for Adverse Events; ctDNA, circulating tumour DNA; EORTC QLQ- C30, European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire; INP , Individualized neoantigen tumor peptides. 6 Wang L, et al.