Brenda De Keersmaecker of eTheRNA Immunotherapies discusses a strong link between T cell activation and durable clinical benefit (DCB) in late stage melanoma patients following vaccination with TriMix and tumor associated antigen mRNA modified dendritic cells plus ipilimumab.
For four cycles, monocyte-derived dendritic cells electroporated with mRNA encoding CD70, CD40 ligand, and constitutively active TLR4 (TriMix), as well as TAAs tyrosinase, gp100, MAGE-A3, and MAGE-C2 were administered along with ipilimumab. A supplementary vaccine was provided for 18/39 patients prior to the first administration of ipilimumab. In previously collected peripheral mononuclear blood cells, which were available for 15 of the patients, TAA-specific T-cell responses were analyzed. Following in vitro T-cell stimulation in 12 patients, vaccine-induced immune responses were observed for this subgroup of patients. Immune responses observed in patients with complete or partial response were substantially stronger and wider, and displayed a higher degree of multifunctionality relative to responses in patients with stable or worsening disease.
Lead author, Dr Brenda De Keersmaecker, commented: “TriMixDC-MEL IPI treatment results in strong vaccine- specific T-cell responses, mainly in patients obtaining durable clinical responses. These results show the power of TriMix-based TAA-specific vaccination in combination with immune checkpoint blockade to break cancer immune tolerance and to give long-term clinical response.”