Based on a first-in-human phase I trial in patients with metastatic melanoma, Hodi et al. reported safety and feasibility of WDVAX, a macroporous poly-lactide-coglycolide matrix polymer scaffold incorporating cytokine GM-CSF, the innate Toll-like receptor 9 agonist CpG oligonucleotide, and autologous tumor lysate. WDVAX showed a favorable safety profile and manufacturing feasibility. Nine patients (42.9%) had stable disease as BOR, with an encouraging 12-month survival estimate of 94%, and a median time-to-progression of 12.4 months. The immune assessments support immunogenicity of the vaccine, with heterogeneous induction of T cells and myeloid cells.
Contributed by Shishir Pant
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.
Author Info: (1) Dana-Farber Cancer Institute, Boston, Massachusetts, United States. (2) Dana-Farber Cancer Institute, Boston, MA, United States. (3) Wyss Institute for Biologically Inspired En
Author Info: (1) Dana-Farber Cancer Institute, Boston, Massachusetts, United States. (2) Dana-Farber Cancer Institute, Boston, MA, United States. (3) Wyss Institute for Biologically Inspired Engineering, United States. (4) Dana-Farber Cancer Institute, Boston, United States. (5) Dana-Farber Cancer Institute, United States. (6) Dana-Farber Cancer Institute, Boston, MA, United States. (7) Dana-Farber Cancer Institute, United States. (8) Dana-Farber Cancer Institute, Boston, MA, United States. (9) Dana-Farber Cancer Institute, Boston, MA, United States. (10) Dana-Farber Cancer Institute, Boston, MA, United States. (11) Attivare Therapeutics Inc., Natick, MA, United States. (12) Wyss Institute for Biologically Inspired Engineering, Boston, United States. (13) Dana-Farber Cancer Institute, Boston, MA, United States. (14) Dana-Farber Cancer Institute, Boston, MA, United States. (15) Dana-Farber Cancer Institute, Boston, United States. (16) Dana-Farber Cancer Institute, Boston, MA, United States. (17) Dana-Farber Cancer Institute, Boston, MA, United States. (18) Brigham and Women's Hospital, Boston, MA, United States. (19) Dana-Farber Cancer Institute, Boston, Massachusetts, United States. (20) Harvard University, Cambridge, MA, United States.
