A phase IB study on intravenous synthetic mRNA electroporated dendritic cell immunotherapy in pretreated advanced melanoma patients
S Wilgenhof, A M T Van Nuffel, D Benteyn, J Corthals, C Aerts, C Heirman, I Van Riet, A Bonehill, K Thielemans, B Neyns, S Wilgenhof, A M T Van Nuffel, D Benteyn, J Corthals, C Aerts, C Heirman, I Van Riet, A Bonehill, K Thielemans, B Neyns
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.
Keywords: TriMixDC-MEL; dendritic cells; immunotherapy; melanoma.
Source: PubMed