S Wilgenhof1, A M T Van Nuffel2, D Benteyn2, J Corthals2, C Aerts2, C Heirman2, I Van Riet3, A Bonehill2, K Thielemans1, B Neyns4. 1. Departments of Medical Oncology; The Laboratory of Molecular and Cellular Therapy and Dendritic Cell Bank of the 'Vrije Universiteit Brussel', Brussels, Belgium. 2. The Laboratory of Molecular and Cellular Therapy and Dendritic Cell Bank of the 'Vrije Universiteit Brussel', Brussels, Belgium. 3. Clinical Hematology UZ Brussel. 4. Departments of Medical Oncology; The Laboratory of Molecular and Cellular Therapy and Dendritic Cell Bank of the 'Vrije Universiteit Brussel', Brussels, Belgium. Electronic address: bart.neyns@uzbrussel.be.
Abstract
BACKGROUND: Autologous monocyte-derived dendritic cells (DCs) electroporated with synthetic messenger RNA (mRNA) encoding a CD40 ligand, a constitutively active Toll-like receptor 4 and CD70, together with mRNA encoding fusion proteins of a human leukocyte antigen (HLA)-class II targeting signal (DC-LAMP) and a melanoma-associated antigen (MAA); either MAGE-A3, MAGE-C2, tyrosinase or gp100) (TriMixDC-MEL) are superiorly immunogenic. PATIENTS AND METHODS: In this phase IB clinical trial, 24 million viable DCs were administered by four biweekly combined intradermal (id) and intravenous (iv) administrations, and a fifth administration on week 16. The number of iv-administered DCs was escalated in four sequentially treated cohorts. Immune responses were assessed by analysis of antigen specificity of blood-derived T-cells and skin infiltrating lymphocytes (SKILs). RESULTS: Fifteen patients with pretreated advanced melanoma tolerated administration of TriMixDC-MEL well. Two patients achieved a complete response and two patients a partial response. All objective responders are progression-free after a follow-up of, respectively, 24+, 28+, 33+, and 34+ months. Post-therapy antigen-specific SKILs were documented in 6 of 12 patients, and antigen-specific CD8(+) T-cells were detected in the blood of 4 of 5 patients. CONCLUSIONS: Cellular immunotherapy with TriMixDC-MEL is safe and immunogenic. Antitumor activity with durable disease control is observed across the investigated iv-dose levels. CLINICALTRIALSGOV IDENTIFIER: NCT01066390.
BACKGROUND: Autologous monocyte-derived dendritic cells (DCs) electroporated with synthetic messenger RNA (mRNA) encoding a CD40 ligand, a constitutively active Toll-like receptor 4 and CD70, together with mRNA encoding fusion proteins of a human leukocyte antigen (HLA)-class II targeting signal (DC-LAMP) and a melanoma-associated antigen (MAA); either MAGE-A3, MAGE-C2, tyrosinase or gp100) (TriMixDC-MEL) are superiorly immunogenic. PATIENTS AND METHODS: In this phase IB clinical trial, 24 million viable DCs were administered by four biweekly combined intradermal (id) and intravenous (iv) administrations, and a fifth administration on week 16. The number of iv-administered DCs was escalated in four sequentially treated cohorts. Immune responses were assessed by analysis of antigen specificity of blood-derived T-cells and skin infiltrating lymphocytes (SKILs). RESULTS: Fifteen patients with pretreated advanced melanoma tolerated administration of TriMixDC-MEL well. Two patients achieved a complete response and two patients a partial response. All objective responders are progression-free after a follow-up of, respectively, 24+, 28+, 33+, and 34+ months. Post-therapy antigen-specific SKILs were documented in 6 of 12 patients, and antigen-specific CD8(+) T-cells were detected in the blood of 4 of 5 patients. CONCLUSIONS: Cellular immunotherapy with TriMixDC-MEL is safe and immunogenic. Antitumor activity with durable disease control is observed across the investigated iv-dose levels. CLINICALTRIALSGOV IDENTIFIER: NCT01066390.
Authors: Yinin Hu; Gina R Petroni; Walter C Olson; Andrea Czarkowski; Mark E Smolkin; William W Grosh; Kimberly A Chianese-Bullock; Craig L Slingluff Journal: Cancer Immunol Immunother Date: 2014-04-23 Impact factor: 6.968
Authors: Fernando Pastor; Pedro Berraondo; Iñaki Etxeberria; Josh Frederick; Ugur Sahin; Eli Gilboa; Ignacio Melero Journal: Nat Rev Drug Discov Date: 2018-09-07 Impact factor: 84.694