A Universal Granulocyte-Macrophage Colony-Stimulating Factor-Producing Bystander Cell Line for Use in the Formulation of Autologous Tumor Cell-Based Vaccines

Abstract

Irradiated tumor cells transduced with the gene encoding the cytokine GM-CSF have been extensively studied as a vaccine formulation capable of priming systemic antitumor immune responses in the tumor-bearing host. In spite of the therapeutic promise of this vaccine strategy demonstrated in both animal models and early-phase clinical trials, clinical development has been limited by difficulties pertaining to the need to establish in culture the tumor of each patient and to perform individualized gene transfer. To circumvent these issues, we generated an HLA-negative human cell line producing large quantities of human GM-CSF for use as a universal bystander cell to be mixed with unmodified autologous tumor cells in the formulation of a vaccine. This line is easily propagated as a suspension culture in defined, serum-free medium. In a mouse model, we find that vaccination with a mixture of autologous tumor cells and an MHC-negative allogeneic GM-CSF-producing bystander cell primes antitumor immune responses that are equivalent or better than those achieved using autologous tumor cells directly transduced to secrete GM-CSF. This strategy greatly simplifies further clinical development of autologous tumor cell-based vaccines.