Efficacy and Safety of PD-1 Blockade-activated Neoantigen Specific Cellular Therapy for Advanced Relapsed Non-small Cell Lung Cancer

Overview

Journal Cancer Immunol Immunother

Specialties Allergy & Immunology
Oncology
Pharmacology

Date 2025 Jan 3

PMID 39751937

Authors

Yun Qiao

Kaiyuan Hui

Chenxi Hu

Mei Wang

Wen Sun

Liang Liu

Changhong Dong

Xiaodong Jiang

Affiliations

Soon will be listed here.

Abstract

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 dendritic cells(mDCs) loaded with neoantigens on day 8 and an intravenous infusion of PD-1 blockade-activated autologous cytotoxic T lymphocytes (CTLs) induced by mDCs on day 27 for a period defined as 28 days (4 weeks). Enrolled patients received at least three 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 relapsed NSCLC were enrolled in this study. All 13 patients received at least three cycles of aNASCT treatment, of which two 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%,95% CI 0.29-0.77).The disease control rate (DCR) was 8 of 13 (61.54%,95% CI 0.36-0.82). 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.

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