TOKYO, JAPAN--(Marketwired - July 25, 2014) - REGiMMUNE Corporation, a biotechnology company focused on the development of immune regulatory therapeutics with its reVax technology, announced that it will present results from its research on its novel approach to long-term tolerance in organ transplantation without continuous administration of immune suppressants at the World Transplant Congress (WTC) on Tuesday, July 29. The poster, "A Novel Approach Inducing Transplant Tolerance by Activated Invariant Natural Killer T Cells with Costimulatory Blockade," will be presented by Toshihito Hirai, MD, Department of Urology, Tokyo Women's Medical University, Tokyo. The WTC acknowledged the importance of REGiMMUNE's research by designating it as one of the top 100 papers submitted (or top 3%) for presentation at this international meeting.
Robust, lifelong, donor-specific tolerance can be reliably achieved by induction of mixed chimerism in various animal models of bone transplantation. To date, the clinical application of these protocols has been impeded by the potential toxicity of the required host conditioning regimens. The REGiMMUNE poster presents the potential of a novel approach using a ligand alpha-GalCer (aGC) for iNKT cells and suboptimal dosage of antibody that blocks CD40:CD40L signaling as a powerful method to generate mixed chimerism. The data suggest a new insight -- that the immune direction of iNKT cells is controlled through a type of APC presenting a-GalCer and costimulation signals, and that it is possible to enhance the innate ability of immune tolerance by appropriate activation of iNKT cells.
REGiMMUNE chief executive officer Yasuyuki Ishii, PhD, commented, "As described in our poster presentation, this combination therapy of aGC liposome with CD40/40L blockade offers great promise and another approach to induce solid organ transplant tolerance -- without continuous administration of immune suppressants -- that may be long lasting."
Abstract: "A Novel Approach Inducing Transplant Tolerance by Activated Invariant Natural Killer T Cells with Co-stimulatory Blockade"
Invariant natural killer T (iNKT) cells are one of the innate lymphocytes that regulate immunity, although it is still elusive how iNKT cells should be manipulated for transplant tolerance. We previously reported that the liposomal formulation of a-galactosylceramide (Lipo-aGC ) could enhance immune-regulative aspect of iNKT cells compared to the conventional aGC. Here we describe a novel approach to induce mixed chimerism (MC ) by activating iNKT cells with Lipo-aGC under CD40-CD40L blockade (MR1). 3Gy irradiated BALB/c mice were transplanted with B6 bone marrow cells (BMC s) with/without Lipo-aGC and/or several dosages of MR1. Only combination therapy of Lipo-aGC plus suboptimal-MR1 showed robust MC. Mice established MC completely accepted subsequent cardiac allografts in a donor-specific manner. High amounts of Th2-cytokines were detected right after iNKT-cell activation, while subsequent IFN-γ production by NK cells was effectively inhibited by MR1. Expansion of regulatory T cells (Tregs) was observed in MC mice and Treg-depletion on 1 day before transplantation resulted MC brake. Further, iNKT-cell knockout mice failed both MC establishment and Tregs expansion. These results collectively suggest that our new protocol makes it possible to induce donor-specific tolerance by enhancement of the innate regulatory mechanism in place of the conventional immunosuppression.
Oral Abstract Session: "Tolerance/Immune Deviation"
Date: Tuesday, 7-29-2014
Time: 11:15 am - 12:45 pm
Publication Number: 1415
Presentation Time: 11:51 am
REGiMMUNE is a biotechnology company focused on the discovery, development and commercialization of immune regulatory therapeutics to treat life-threatening and debilitating conditions, including allergies, autoimmune diseases and transplantation. The company's proprietary platform technology, reVax, induces immune tolerance in an antigen-specific manner through pharmacological induction of regulatory T (Treg) cells. Using its reVax technology, REGiMMUNE is developing RGI-2001, which may be the first drug in the class of Treg-inducing agents.
The company is also applying its reVax technology to develop a range of pipeline products, including its RGI-1000 series for allergy and its RGI-3100 series for type 1 diabetes. Additionally REGiMMUNE is developing products for preventing inhibitor formation in enzyme replacement therapies (ERT) and for celiac disease with undisclosed partners. The company is seeking pharmaceutical partnership opportunities for its products worldwide, exclusive of Japan. REGiMMUNE is headquartered in Tokyo, Japan and has a US operation in San Francisco, California. For more information, visit www.regimmune.com.