Menlo Park, Calif.-based Geron Corporation (GERN) said on November 13 that a new study shows that its 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 research conducted by Ross Okamura, Ph.D. and other Geron scientists suggests 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, Geron said.
The results also support the position that patient-specific hESC lines are not needed to prevent immune rejection.
GRNOPC1 cells are minimally recognized by both the innate (natural killer) and adaptive (cytotoxic T cell) arms of the human immune system, according to the study.
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 CEO Thomas Okarma. "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.
The 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 gamma-interferon or TNF-alpha, allogeneic T cell proliferation was not induced.
In addition, GRNOPC1 cells were not lysed by natural killer cells, the "innate" arm of the immune system.
GRNOPC1 cells were also largely resistant to killing by antibodies present in the sera of normal healthy individuals.
Sera from eight of 10 individuals failed to induce the killing of GRNOPC1 cells.
The sera from the remaining two individuals induced only 10 percent GRNOPC1 cell lysis.
GRNOPC1 is an allogeneic population of cells containing oligodendroglial progenitors intended for transplantation into the lesion site of patients with spinal cord injury to induce tissue repair.
Geron's development plan for the product calls for the filing of an Investigational New Drug (IND) Application with the U.S. Food and Drug Administration and, pending the agency's review, initiation of human clinical trials in 2008.
Geron is developing human embryonic stem cell-based therapeutics, with its spinal cord injury treatment anticipated to be the first product to enter clinical development.
Contact: http://www.geron.com
