Therapeutic cancer vaccine: phase I clinical tolerance study of Hu-rhEGF-rP64k/Mont in patients with newly diagnosed advanced non-small cell lung cancer

Abstract

BackgroundHu-rhEGF-rP64k/Mont is a biotechnology product for the treatment of advanced non-small cell lung cancer (NSCLC). The vaccine induces a neutralizing antibody-mediated immune response, against the normal circulating self-protein antigen epidermal growth factor (EGF), which prevents its binding to and activation of the EGF receptor, inhibiting the transduction of the signals that drive cancer cell proliferation, survival and spread. This phase I study aimed to evaluate the safety and the immunological response of Hu-rhEGF-rP64k vaccine in NSCLC patients.ResultsThe Hu-rhEGF-rP64k/Mont vaccine showed to be safe and well tolerated, with dizziness, injection-site reactions and tremors being the most commonly reported adverse event. No severe adverse events or death were related to the vaccination. Immune monitoring demonstrated the generation of anti-EGF antibody titers and as a consequence the patients exhibited a decrease in the EGF concentration. In 80% of the vaccinated patients stable disease was achieved.ConclusionHu-rhEGF-rP64k/Mont elicited a valuable immune response, with good safety profile assuring further clinical development of the vaccine in this population to further confirm the potential benefits on survival.Trial registrationChinese Clinical Trial Registry, ChiCTR-OID-17014048, date 2017/12/20 (retrospectively registered); Chinese Food and Drug Administration, CFDA 2009 L02105, date 2009/04/03; China Drug Trial, CTR20131039.

Emerging Vaccine Immunotherapy In NSCLC: The Adverse Reactions of Recent Clinical Trials and Future Directions

“…Over the past five years (2017-2021), 15 lung cancer vaccine research projects have been reported worldwide [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. Most of the projects are in Phase I to II trials, only one is in the experimental development phase and the other is in the improvement phase.…”

“…In this experiment, 14 cases (66.67% of 48 cases) reported adverse events, mainly in grade I/II, and 1 case in grade III. The researchers believe that the adverse reactions in some of these cases may be related to previous chemotherapy [33]. Another phase I trial of intratumoural injection of autologous DC (AdCCL21-DC) overexpressing CCL21 found that influenza-like symptoms and bloody sputum, nausea and fatigue were common symptoms.…”

Immunotherapy in the First-Line Treatment of NSCLC: Current Status and Future Directions in China

“…However, patients with NSCLC lacking driver mutations do not benefit from targeted therapies (20,21). ICIs, adoptive T cell therapies, cytokineinduced killer cells, and other emerging immunotherapies are transforming the treatment of NSCLC, especially those lacking driver mutations (9,(22)(23)(24)(25)(26).…”

Overview of Lung Cancer Immunotherapy

“…In the last decades, multiple vaccination strategies have been developed for lung cancer patients (Table 1). [21][22][23][24][25][26][27][28][29][30]32,[34][35][36][37][38][39][40] However, modest clinical outcomes, complex manufacturing processes, and the recent advent immune checkpoint blockers have limited their clinical impact. Modern personalized neoepitope-based strategies 31,33 and combination with checkpoint blockers might reactivate this therapeutic modality in the future.…”