Use of DENdritic cells in vaccine delivery and human embryonic stem cell therapies

Dr Colin Story , Life Sciences Group, Isis Innovation Ltd

In March 2006 Geron Corporation entered into a worldwide exclusive licence agreement covering patent applications describing a method for generating dendritic cells (“DCs”) from human embryonic stem cells (“hESCs”).  In a linked research agreement, Geron will fund work in the University’s Sir William Dunn School of Pathology to further develop the technology under the guidance of Dr. Paul Fairchild and Professor Herman Waldmann.

DCs are specialized cells of the immune system that have several functions of potential therapeutic significance.  In one form, DCs are highly effective in presenting foreign antigens to the immune system to initiate an immune response against the source of those antigens, such as an invading pathogen or a tumor.  Geron’s GRNVAC1 cancer vaccine consists of dendritic cells isolated from patients and pulsed with RNA encoding telomerase, an antigen that is highly expressed in nearly all cancer cells.  This vaccine has demonstrated safety and induction of a beneficial immune response against telomerase in Phase 1 clinical trials conducted at Duke University.  In a future product, the scalable production of dendritic cells from hESCs could serve as an alternative to isolating DCs from each patient, and possibly as a broadly useful vaccine delivery vehicle.

In another form, DCs may act to block an immune response against an antigen by teaching the immune system not to attack it - a process known as “tolerizing” the individual to that antigen.  In organ transplant studies where bone marrow cells from the organ donor are given to the recipient along with the organ, such a tolerizing effect has been observed – patients receiving such double transplants have a reduced risk of their immune systems rejecting the transplanted organ.  This permits physicians to reduce, or potentially eliminate, the need for transplant patients to receive long-term immunosuppressive drugs to avoid organ rejection.  Geron believes a similar approach may enable immune tolerance for its hESC-based cell therapies, including cardiomyocytes for heart failure, pancreatic islets for diabetes, and oligodendrocytes for spinal cord injury.  Since the same pluripotent hESC line could be used to generate both tolerizing DCs and the therapeutic cells, co-administration of these two cell populations could potentially circumvent immune rejection without the need for immunsuppressive drugs.

The license agreement provides Geron with exclusive rights to the patent applications already filed for the Oxford technology, as well as inventions arising from the collaborative research that Geron will fund at Oxford.  “The license agreement provides Geron with worldwide exclusive rights across all fields, which will serve both to protect Geron’s investment in developing products based on this technology and also to provide the opportunity to license other companies interested in developing applications of the technology.” noted David J. Earp, J.D., Ph.D., Geron’s senior vice president of business development and chief patent counsel.

Tom Hockaday, Executive Director Isis Innovation Ltd commented:  "We are pleased with the relationship with Geron; it is a good example of Oxford's strength in university-business collaborations, with Isis commercialising existing University technologies with a business partner who also funds additional research in the University aimed at developing new improved healthcare technologies."