Efficacy and Safety of MUC1 Antigen-Specific Vaccine as a Breakthrough Solution in the Treatment of Advanced Non-Small Cell Lung Cancer
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Abstract
Introduction: Non-Small Cell Lung Cancer (NSCLC) is the leading cause of death for cancer patients globally. Most of the patients are diagnosed in advanced stage that can only receive conventional chemotherapy with low overall survival and low progression-free survival outcomes. With the advancement of technology, researchers have discovered that antigen-specific vaccine could be utilized to fight tumor cells. MUC1 antigen-specific vaccine is a novel solution that has been proved to be specific and accurate against NSCLC. In this study, we would like to present current best evidences regarding the efficacy and safety of MUC1 antigen specific vaccine in battling NSCLC.
Methods: Literature search was conducted on databases, namely PubMed, Scopus, Cochrane, Science Direct, EBSCOhost, and Google Scholar up to August 27th 2022. Our inclusion criteria include randomized controlled trials in patients with advanced stage NSCLC, given MUC1 antigen-specific vaccine as treatment, compared to placebo as control group, and measured the efficacy in terms of overall survival and progression-free survival, quality of life, and adverse events.
Results and discussion: Six randomized controlled trials were included in this review. Overall, longer overall survival and progression-free survival is observed in all studies. However, significance differed from study to study. This could be attributed to different patient characteristics and chemotherapy regimens used. MUC1 antigen-specific vaccine is more effective in patients who received concurrent chemoradiotherapy, high sMUC1 and ANA level, and non-squamous tumor type. Minimum adverse events were reported and incidence is similar with the control group. No negative impact on quality of life was observed.
Conclusion: MUC1 vaccine showed a promising impact on improving patients’ overall survival and progression-free survival while ensuring patient’s safety. However, further studies with larger sample size are recommended on more specific populations, for instance, patients with concurrent chemotherapy.
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References
I. Geraci E, Chablani L. Immunotherapy as a second-line or later treatment modality for advanced non-small cell lung cancer: A review of safety and efficacy. Crit Rev Oncol Hematol. 2020;152(May):103009.
II. Zarogoulidis K, Zarogoulidis P, Darwiche K, Boutsikou E, Machairiotis N, Tsakiridis K, et al. Treatment of non-small cell lung cancer (NSCLC). J Thorac Dis. 2013;5(Suppl 4):S389.
III. Rotonda C, Anota A, Mercier M, Bastien B, Lacoste G, Limacher JM, et al. Impact of TG4010 vaccine on health-related quality of life in advanced non-small-cell lung cancer: Results of a phase IIB clinical trial. PLoS One. 2015;10(7):1–13.
IV. Butts C, Socinski MA, Mitchell PL, Thatcher N, Havel L, Krzakowski M, et al. Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): A randomised, double-blind, phase 3 trial. Lancet Oncol. 2014;15(1):59–68.
V. Katakami N, Hida T, Nokihara H, Imamura F, Sakai H, Atagi S, et al. Phase I/II study of tecemotide as immunotherapy in Japanese patients with unresectable stage III non-small cell lung cancer. Lung Cancer. 2017;105:23–30.
VI. Quoix E, Lena H, Losonczy G, Forget F, Chouaid C, Papai Z, et al. TG4010 immunotherapy and first-line chemotherapy for advanced non-small-cell lung cancer (TIME): Results from the phase 2b part of a randomised, double-blind, placebo-controlled, phase 2b/3 trial. Lancet Oncol. 2016;17(2):212–23.
VII. Tagliamonte M, Petrizzo A, Tornesello ML, Buonaguro FM, Buonaguro L. Antigen-specific vaccines for cancer treatment. Hum Vaccin Immunother. 2014 Nov 1;10(11):3332–46.
VIII. Leclerc M, Mezquita L, De Nerville GG, Tihy I, Malenica I, Chouaib S, et al. Recent advances in lung cancer immunotherapy: Input of T-cell epitopes associated with impaired peptide processing. Front Immunol. 2019;10(JUL):1505.
IX. Cortés-Jofré M, Uranga R, Pombert AT, Arango Prado MDC, Aguirrechu IC, Pacheco C, et al. Therapeutic vaccines for advanced non-small cell lung cancer. Cochrane Database Syst Rev. 2019 Aug 1;2019(8).
X. Lakshmanan I, Ponnusamy MP, Macha MA, Haridas D, Majhi PD, Kaur S, et al. Mucins in Lung Cancer: Diagnostic, Prognostic, and Therapeutic Implications. J Thorac Oncol. 2015 Jan 1;10(1):19–27.
XI. Gao T, Cen Q, Lei H. A review on development of MUC1-based cancer vaccine. Biomed Pharmacother. 2020 Dec 1;132:110888.
XII. Ning Y, Zheng H, Zhan Y, Liu S, Yang Y, Zang H, et al. Comprehensive analysis of the mechanism and treatment significance of Mucins in lung cancer. J Exp Clin Cancer Res. 2020 Aug 17;39(1):1–10.
XIII. Raina D, Kosugi M, Ahmad R, Panchamoorthy G, Rajabi H, Alam M, et al. Dependence on the MUC1-C Oncoprotein in Non-Small Cell Lung Cancer Cells. Mol Cancer Ther. 2011 May;10(5):806.
XIV. Saltos A, Khalil F, Smith M, Li J, Schell M, Antonia SJ, et al. Clinical associations of mucin 1 in human lung cancer and precancerous lesions. Oncotarget. 2018 Nov 11;9(86):35666.
XV. Jeon JM, Lee HW, Park JY, Jung HR, Hwang I, Kwon SY, et al. Expression of MUC1 and MUC4 and Its Prognostic Significance in Non-Small Cell Lung Carcinoma. Korean J Pathol. 2010 Aug;44(4):397–403.
XVI. Situ D, Wang J, Ma Y, Zhu Z, Hu Y, Long H, et al. Expression and prognostic relevance of MUC1 in stage IB non-small cell lung cancer. Med Oncol. 2011 Dec;28 Suppl 1(SUPPL. 1).
XVII. Xu T, Li D, Wang H, Zheng T, Wang G, Xin Y. MUC1 downregulation inhibits non-small cell lung cancer progression in human cell lines. Exp Ther Med. 2017 Nov 1;14(5):4443–7.
XVIII. Ham SY, Kwon T, Bak Y, Yu JH, Hong J, Lee SK, et al. Mucin 1-mediated chemo-resistance in lung cancer cells. Oncog 2016 51. 2016 Jan 18;5(1):e185–e185.
XIX. Szabo E. MUC1 expression in lung cancer. Methods Mol Med. 2003;74:251–8.
XX. Tosch C, Bastien B, Barraud L, Grellier B, Nourtier V, Gantzer M, et al. Viral based vaccine TG4010 induces broadening of specific immune response and improves outcome in advanced NSCLC. J Immunother Cancer. 2017;5(1):1–10.
XXI. Mitchell PL, Thatcher N, Socinski MA, Wasilewska-Tesluk E, Horwood K, Szczesna A, et al. Tecemotide in unresectable stage III non-small-cell lung cancer in the phase III START study: Updated overall survival and biomarker analyses. Ann Oncol. 2015;26(6):1134–42.
XXII. Gelbard A, Garnett CT, Abrams SI, Patel V, Gutkind JS, Palena C, et al. Combination Chemotherapy and Radiation of Human Squamous Cell Carcinoma of the Head and Neck Augments CTL-Mediated Lysis. Clin Cancer Res. 2006 Mar 3;12(6):1897.
XXIII. Hillman GG, Reich LA, Rothstein SE, Abernathy LM, Fountain MD, Hankerd K, et al. Radiotherapy and MVA-MUC1-IL-2 vaccine act synergistically for inducing specific immunity to MUC-1 tumor antigen. J Immunother Cancer. 2017 Jan 17;5(1):1–13.
XXIV. Ramlau R, Quoix E, Rolski J, Pless M, Lena H, Lévy E, et al. A phase II study of Tg4010 (Mva-Muc1-Il2) in association with chemotherapy in patients with stage III/IV non-small cell lung cancer. J Thorac Oncol. 2008;3(7):735–44.