Geron Corporation has announced the publication of study results showing that GRNOPC1, the company’s human embryonic stem cell (hESC)-based therapeutic for the treatment of spinal cord injury, evades direct attack by the human immune system in vitro.
Published in the November online issue of the Journal of Neuroimmunology, the results of research conducted by Ross Okamura, Ph.D. and other Geron scientists suggest that unlike whole organ transplants, cellular therapeutics derived from hESCs may provoke only minimal immune reactions and that rejection may be controlled or prevented by short courses of low-dose immunosuppressive drugs. The results also support the position that patient-specific hESC lines are not needed to prevent immune rejection.
Specifically, the research findings demonstrate that GRNOPC1 cells are minimally recognized by both the innate (natural killer) and adaptive (cytotoxic T cell) arms of the human immune system.
In addition, the data show that the cells are resistant to lysis by human serum containing anti-Neu5Gc antibodies, which some scientists believed was problematic for any hESC line derived on mouse feeders.
Geron’s oligodendroglial progenitors express HLA class I antigen but not class II markers, even after stimulation by inflammatory cytokines. Analysis of factors secreted by these cells in the presence of inflammatory cytokines show the induction of several ligands, including B7-H1, which have been previously shown to enhance successful engraftment across allogeneic barriers.
“We published evidence in 2004 showing that undifferentiated hESCs are immunoprivileged, which means they are minimally recognized by allogeneic human immune cells in vitro,” said Thomas B. Okarma, Ph.D., M.D., Geron’s president and CEO.
“This publication shows that the same immune-privileged properties are displayed by differentiated progeny of hESCs. In this case, they are oligodendroglial progenitors for acute spinal cord injury. More importantly, the study results suggest a possible reduction in the requirement for immunosuppressive drugs in patients treated with OPC1 cells. This should minimize the potential for side effects often attributed to these agents.”
In the studies, GRNOPC1 cells were tested for susceptibility to both immune effector cells and sera from multiple allogeneic normal healthy individuals. GRNOPC1 cells stimulated very low levels of T cell proliferation. Allogeneic T cell proliferation is a standard measure of immune recognition of foreign transplanted tissue. Even when GRNOPC1 cells were exposed to proinflammatory cytokines, such as beta-interferon or TNF-alpha, allogeneic T cell proliferation was not induced.