PD-1 Blockade-activated Neoantigen Specific Cellular Therapy For Advanced Relapsed Non Small Cell Lung Cancer
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Background Due to its strong immunogenicity and tumor specificity, neoplastic antigen has emerged as an immunotherapy target with wide therapeutic prospect and clinical application value. Anti-programmed death-1 (PD-1) antibodies reinvigorate T cell-mediated antitumor immunity .So we conducted single-arm trial to assess the safety and efficacy of PD-1 blockade(Camrelizumab)-activated Neoantigen Specific Cellular Therapy (aNASCT) on advanced relapsed non-small lung cancer( NSCLC)(ClinicalTrials.gov NCT03205930). Methods Neoantigenic peptides were designed and manufactured according to the whole-exome sequencing and RNA sequencing of fresh biopsy tissues and peripheral blood as well as bioinformatics analysis.All participants received subcutaneous injection of mature DCS (mDCS) loaded with neoantigens on day 8 and subcutaneous injection of mDC-induced autologous somatic toxic T lymphocytes (CTLS) on day 27 for a period defined as 28 days (4 weeks). Enrolled patients received at least 3 cycles of therapy.The safety and efficacy of the treatment were evaluated by evaluating adverse reactions, progression-free survival (PFS), overall survival (OS). Results A total of 13 patients with advanced replased NSCLC were enrolled in this study. All 13 patients received at least 3 cycles of aNASCT treatment, of which 2 patients received at most 12 cycles of treatment. Treatment-related adverse events (AEs) occurred in 4/13 (30.8%)patients with transient fever below 38℃.The objective response rate (ORR) across the 13 enrolled patients was 7 of 13 (53.85%).The disease control rate (DCR) was 8 of 13 (61.54%). The median PFS was 11 months (95% CI 6.1–15.9), and the median OS was 15 months(95% CI 11.5–18.5). Conclusions Our findings indicate that aMASCT therapy was safety and immunogenicity of patients with advanced relapsed NSCLC, suggesting its promising potential in cancer immunotherapy.