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

Abstract The optimal means to prime for effective antitumor immunity in a patient with cancer remain elusive in the current era of checkpoint blockade. Crafting a strategy to amplify the number and function of 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. Herein, we report data from a phase I trial in patients with metastatic melanoma who received the cytokine GM-CSF and the innate Toll-like receptor 9 agonist CpG oligonucleotide admixed with autologous tumor lysate onto a microporous poly-lactide-co-glycolide matrix polymer scaffold that achieves precise control over the spatial and temporal release of immunostimulatory agents in vivo. This materials system (WDVAX) served as a physical antigen-presenting structure to which dendritic cells and other immune-stimulating cells are recruited and activated. In this first clinical trial of a macroscale biomaterial–based vaccine, WDVAX treatment was found to be feasible and to induce immune activation in patients with melanoma.