Geron Presents Data at ISSCR Showing That Its Embryonic Stem Cell Therapeutic for Heart Failure Evades Direct Attack by the Human Immune System
The data presented at the International Society for Stem Cell Research (ISSCR) Annual Meeting indicate that, unlike whole organ transplants, cell therapies derived from hESCs may provoke only minimal immune reactions suggesting that rejection may be controlled or prevented by short courses of low-dose immunosuppressive drugs. The work also suggests that patient-specific hESC lines may not be needed to prevent immune rejection.
"We published evidence in 2007 demonstrating the immune-privileged properties of GRNOPC1, our hESC-derived oligodendroglial progenitor cell therapeutic for acute spinal cord injury," said Thomas B Okarma, Ph.D., M.D., Geron's president and chief executive officer. "We now have evidence that a second hESC-derived therapeutic cell type, cardiomyocytes for the treatment of heart failure, displays the same properties in vitro. These results suggest that patients treated with GRNCM1 may only require a short course of low-dose immunosuppression which decreases the possibility of unwanted side effects commonly associated with those types of drugs."
The data presented show that GRNCM1 expresses HLA class I antigen on their surface, but not HLA class II, or other surface markers required for T-cell activation, even after stimulation by inflammatory cytokines. In these studies, GRNCM1 cells were tested for susceptibility to immune effector cells and sera from several allogeneic normal healthy individuals. GRNCM1 cells did not stimulate the proliferation of T cells in vitro, a standard measure of immune recognition of foreign transplanted tissue. Even when GRNCM1 cells were exposed to proinflammatory cytokines, such as gamma-interferon or TNF-alpha, allogeneic T cell proliferation was not induced. In addition, GRNCM1 cells were largely resistant to killing by sera of normal healthy individuals.
Additional presentations by Geron collaborators from the University of Edinburgh, Scotland, demonstrated 1) successful engraftment of hESC-derived hepatocytes in mice, 2) engraftment of hESC-derived osteogenic cells in rat calvarial defects and 3) repair of rodent knee cartilage defects by hESC-derived cartilage progenitor cells.
"We are pleased with the progress of our collaborators at the University of Edinburgh who have advanced three additional hESC-derived therapeutic cell types into early animal feasibility studies," continued Dr. Okarma. "This work is supported by a recently awarded $7.2 million grant to the University of Edinburgh from the UK Stem Cell Foundation."
Presentations on hESC-Derived Hepatocytes
Geron collaborators at the University of Edinburgh led by Dr. John Iredale presented studies that demonstrated survival of hESC-derived hepatocytes injected into the livers and spleens of immune-compromised mice for up to 31 days. The surviving cells produced human albumin, which was also detectable in the serum of the transplanted mice. These studies provide early evidence that hESC-derived hepatocytes may have application for the treatment of liver failure.
Presentations on hESC-Derived Chondrocytes
Geron collaborators at the University of Edinburgh led by Dr. Brendon Noble presented studies examining the engraftment of hESC-derived chondrogenic and osteogenic progenitor cells in rodents with cartilage or bone defects. hESC-derived chondroprogenitor cells that expressed type II collagen were implanted into an articular chondral defect in the knees of rats. Human cells were detected within the regenerating cartilage at 21 days, and histological analysis indicated a significantly improved overall grading of the repair compared to untreated controls or animals implanted with progenitors derived from human bone marrow stromal cells. These early results suggest that hESC-derived cartilage progenitors may have application in cartilage repair.
Presentations on hESC-Derived Osteoblasts
In separate studies, hESC-derived osteogenic progenitors were implanted into rat calvarial lesions. Human cells were detected at 14 days and there was a significant increase in newly mineralized tissue compared to controls, demonstrating bone regeneration by these cells.
Geron is developing first-in-class biopharmaceuticals for the treatment of cancer and chronic degenerative diseases, including spinal cord injury, heart failure and diabetes. The company is advancing an anti-cancer drug and a cancer vaccine that target the enzyme telomerase through multiple clinical trials. Geron is also the world leader in the development of human embryonic stem cell-based therapeutics, with its spinal cord injury treatment anticipated to be the first product to enter clinical development. For more information, visit www.geron.com.
This news release may contain forward-looking statements made pursuant to the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that statements in this press release regarding potential applications of Geron's human embryonic stem cell technology constitute forward-looking statements that involve risks and uncertainties, including, without limitation, risks inherent in the development and commercialization of potential products, uncertainty of clinical trial results or regulatory approvals or clearances, need for future capital, dependence upon collaborators and maintenance of our intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements. Additional information on potential factors that could affect our results and other risks and uncertainties are detailed from time to time in Geron's periodic reports, including the quarterly report on Form 10-Q for the quarter ended March 31, 2008.
Posted: June 2008