A randomized controlled phase II clinical trial on mRNA electroporated autologous monocyte-derived dendritic cells (TriMixDC-MEL) as adjuvant treatment for stage III/IV melanoma patients who are disease-free following the resection of macrometastases

Yanina Jansen1, Vibeke Krüse2, Jurgen Corthals3, Kelly Schats4, Pieter-Jan van Dam4, Teofila Seremet1, Carlo Heirman3, Liève Brochez2, Mark Kockx4, Kris Thielemans3, Bart Neyns1
1Department of Medical Oncology, Universitair Ziekenhuis Brussel (UZ Brussel), Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090, Brussels, Belgium
2Department of Medical Oncology, Universitair Ziekenhuis Gent (UZ Gent), Ghent, Belgium
3Laboratory of Molecular and Cellular Therapy and Dendritic Cell-bank, Vrije Universiteit Brussel, Brussels, Belgium
4Histogenex NV, Antwerp, Belgium

Tóm tắt

Từ khóa


Tài liệu tham khảo

Ayers M, Lunceford J, Nebozhyn M, Murphy E, Loboda A, Kaufman DR et al (2017) IFN-γ–related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest 127(8):2930–2940. https://doi.org/10.1172/JCI91190

Balch CM, Gershenwald JE, Soong S et al (2010) Multivariate analysis of prognostic factors among 2,313 patients with stage III melanoma: comparison of nodal micrometastases versus macrometastases. J Clin Oncol 28:2452–2459. https://doi.org/10.1200/JCO.2009.27.1627

Bol KF, Aarntzen EHJG, in’t Hout FEM et al (2016) Favorable overall survival in stage III melanoma patients after adjuvant dendritic cell vaccination. Oncoimmunology 5:1–8. https://doi.org/10.1080/2162402X.2015.1057673

Bonehill A, Tuyaerts S, Van Nuffel AMT et al (2008) Enhancing the T-cell stimulatory capacity of human dendritic cells by co-electroporation with CD40L, CD70 and constitutively active TLR4 encoding mRNA. Mol Ther 16:1170–1180. https://doi.org/10.1038/mt.2008.77

Bonehill A, Van Nuffel AMT, Corthals J et al (2009) Single-step antigen loading and activation of dendritic cells by mRNA electroporation for the purpose of therapeutic vaccination in melanoma patients. Clin Cancer Res 15:3366–3375. https://doi.org/10.1158/1078-0432.CCR-08-2982

Byrd DR, Sondak VK, Soong S et al (2009) Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 27:6199–6206. https://doi.org/10.1200/jco.2009.23.4799

Carrasco J, Van Pel A, Neyns B et al (2014) Vaccination of a melanoma patient with mature dendritic cells pulsed with MAGE-3 peptides triggers the activity of nonvaccine anti-tumor cells. J Immunol 180:3585–3593. https://doi.org/10.4049/jimmunol.180.5.3585

Daud AI, Wolchok JD, Robert C et al (2016) Programmed death-ligand 1 expression and response to the anti-programmed death 1 antibody pembrolizumab in melanoma. J Clin Oncol 34:4102–4109. https://doi.org/10.1200/JCO.2016.67.2477

Eggermont AMM, Blank CU, Mandala M et al (2018) Adjuvant pembrolizumab versus placebo in resected stage III melanoma. N Engl J Med 378:1789–1801. https://doi.org/10.1056/NEJMoa1802357

Eggermont AMM, Chiarion-Sileni V, Grob J-J et al (2016) Prolonged survival in stage III melanoma with ipilimumab adjuvant therapy. N Engl J Med 375:1845–1855. https://doi.org/10.1056/NEJMoa1611299

Long GV, Hauschild A, Santinami M et al (2017) Adjuvant dabrafenib plus trametinib in stage III BRAF-mutated melanoma. N Engl J Med 377:1813–1823. https://doi.org/10.1056/nejmoa1708539

Markowicz S, Nowecki ZI, Rutkowski P et al (2012) Adjuvant vaccination with melanoma antigen-pulsed dendritic cells in stage III melanoma patients. Med Oncol 29:2966–2977. https://doi.org/10.1007/s12032-012-0168-1

Mocellin S, Lens MB, Pasquali S et al (2013) Interferon alpha for the adjuvant treatment of cutaneous melanoma. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.cd008955.pub2

Ollila DW (2006) Complete metastasectomy in patients with stage IV metastatic melanoma. Lancet Oncol 7:919–924. https://doi.org/10.1016/S1470-2045(06)70938-X

Romano E, Scordo M, Dusza SW et al (2010) Site and timing of first relapse in stage III melanoma patients: implications for follow-up guidelines. J Clin Oncol 28:3042–3047. https://doi.org/10.1200/JCO.2009.26.2063

Van Nuffel AMT, Benteyn D, Wilgenhof S et al (2012) Dendritic cells loaded with mRNA encoding full-length tumor antigens prime CD4 + and CD8 + T cells in melanoma patients. Mol Ther 20:1063–1074. https://doi.org/10.1038/mt.2012.11

Van Nuffel AMT, Benteyn D, Wilgenhof S et al (2012) Intravenous and intradermal TriMix-dendritic cell therapy results in a broad T-cell response and durable tumor response in a chemorefractory stage IV-M1c melanoma patient. Cancer Immunol Immunother 61:1033–1043. https://doi.org/10.1007/s00262-011-1176-2

Weber J, Mandala M, Del Vecchio M et al (2017) Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. N Engl J Med 377:1824–1835. https://doi.org/10.1056/NEJMoa1709030

Wilgenhof S, Corthals J, Heirman C et al (2016) Phase II study of autologous monocyte-derived mRNA electroporated dendritic cells (TriMixDC-MEL) plus ipilimumab in patients with pretreated advanced melanoma. J Clin Oncol 34:1330–1338. https://doi.org/10.1200/JCO.2015.63.4121

Wilgenhof S, Corthals J, Van Nuffel AMT et al (2015) Long-term clinical outcome of melanoma patients treated with messenger RNA-electroporated dendritic cell therapy following complete resection of metastases. Cancer Immunol Immunother 64:381–388. https://doi.org/10.1007/s00262-014-1642-8

Wilgenhof S, Van Nuffel AMT, Benteyn D et al (2013) A phase IB study on intravenous synthetic mRNA electroporated dendritic cell immunotherapy in pretreated advanced melanoma patients. Ann Oncol Off J Eur Soc Med Oncol 24:2686–2693. https://doi.org/10.1093/annonc/mdt245

Wilgenhof S, Van Nuffel AMT, Corthals J et al (2011) Therapeutic vaccination with an autologous mRNA electroporated dendritic cell vaccine in patients with advanced melanoma. J Immunother 34:448–456. https://doi.org/10.1097/CJI.0b013e31821dcb31