Geron reports that dendritic cells (DCs) scalably manufactured from human embryonic stem cells (hESCs) exhibit normal functions of naturally occurring human DCs found in the bloodstream. These findings support the use of hESC-derived DCs in therapeutic vaccine applications for cancer and other infectious diseases, which is the firm’s core focus.
The study appears online in advance of print in the journal Regenerative Medicine. The paper is titled “Generation of immunogenic dendritic cells from human embryonic stem cells without serum and feeder cells.”
“We are using a DC platform with our cancer vaccine directed against a telomerase, GRNVAC1, currently in Phase II studies in AML,” says Thomas B. Okarma, Ph.D., M.D., Geron's president and CEO.
“However, GRNVAC1 and other therapies currently in development use DCs that are generated from individual patients. Autologous cell treatments are costly to manufacture and difficult to control. Variation between individuals and the effects of their disease and prior treatments can affect vaccine potency. We are therefore developing a second-generation cancer vaccine, GRNVAC2, based on DCs derived from hESCs to generate a scalable, reliable, off-the-shelf product free from individual patient variability.”
Geron was able to show that immature hESC-derived DCs could take up, process, and present antigens. Following maturation in the manufacturing process, the DCs were also able to migrate, produce proinflammatory cytokines, and induce specific immune responses to both tumor and viral antigens in vitro.
Geron’s experiments were able to create mature hESC-derived DCs that produced a number of cytokines important for T-cell stimulation, including IL-12p70, and stimulated allogeneic T-cell proliferation when co-cultured with peripheral blood mononuclear cells in a mixed leukocyte response (MLR) assay.
Another key function of DCs is their ability to migrate from the site of antigen uptake to the lymph nodes in response to chemical signals. Migratory response of mature hESC-derived DCs in the study was comparable to peripheral blood monocyte-derived DCs in an in vitro chemotactic assay using the chemokine MIP3â.
When a dendritic cell presents an antigen to a T cell in vivo, it stimulates the T cell to produce inflammatory cytokines and causes antigen-specific T-cell proliferation. In the current study using mumps, cytomegalovirus, and telomerase antigens in three separate series of experiments, the hESC-derived DCs stimulated antigen-specific T-cell proliferation in each case, a prerequisite for effective in vivo immunotherapy.