First-in-Human Clinical Trial of Vaccination with WDVAX, a Dendritic Cell Activating Scaffold Incorporating Autologous Tumor Cell Lysate, in Metastatic Melanoma Patients

Abstract The optimal means to prime for effective anti-tumor immunity in a cancer patient remains elusive in the current era of checkpoint blockade. Crafting a strategy to amplify CD8+ T cells while blocking regulatory cells should increase immunotherapy efficacy. Biomaterial carriers have been demonstrated in preclinical studies to amplify the effects of immunomodulatory agents, synergistically integrate the effects of different agents, and concentrate and manipulate immune cells in vivo. In this phase I trial in patients with metastatic melanoma, the cytokine GM-CSF and the innate TLR9 agonist CpG oligonucleotide were admixed with autologous tumor lysate onto a microporous poly-lactide-co-glycolide (PLG) matrix polymer scaffold that achieves precise control over the spatial and temporal release of immunostimulatory agents in vivo. This materials system served as a physical antigen-presenting structure for which dendritic cells and other immune-stimulating cells are recruited and activated (WDVAX). In this first clinical trial of a macroscale biomaterial-based vaccine, WDVAX treatment was found to be feasible and induced immune activation in melanoma patients.