A universal granulocyte-macrophage colony-stimulating factor-producing bystander cell line for use in the formulation of autologous tumor cell-based vaccines
I. Borrello et al., A universal granulocyte-macrophage colony-stimulating factor-producing bystander cell line for use in the formulation of autologous tumor cell-based vaccines, HUM GENE TH, 10(12), 1999, pp. 1983-1991
Irradiated tumor cells transduced with the gene encoding the cytokine GM-CS
F 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 anim
al models and early-phase clinical trials, clinical development has been li
mited by difficulties pertaining to the need to establish in culture the tu
mor of each patient and to perform individualized gene transfer, To circumv
ent these issues, we generated an HLA-negative human cell line producing la
rge 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 vaccin
e, 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 byst
ander cell primes antitumor immune responses that are equivalent or better
than those achieved using autologous tumor cells directly transduced to sec
rete GM-CSF. This strategy greatly simplifies further clinical development
of autologous tumor cell-based vaccines.