Public HealthArgos Therapeutics Presents Positive Transplantation And Immunosuppression Data For Soluble CD83 At The American Transplant Congress
Argos Therapeutics announced the presentation of new information on its soluble CD83 (sCD83) protein program in a poster session at the 2009 American Transplant Congress, held May 30-June 3 in Boston. The poster presentation, to be made on June 2 at 5:30pm by Argos" collaborating scientists from the University of Western Ontario, demonstrates that combination therapy with sCD83 can prolong kidney allograft survival in an animal model of transplantation, and that sCD83 attenuates pathological changes in kidney allografts, induces generation of T regulatory cells and inhibits dendritic cell maturation, all of which may contribute to immunosuppression and allograft tolerance.
In the study, researchers tested the safety and immunosuppressive efficacy of sCD83 alone and in combination with rapamycin in a preclinical allograft model. Kidney allografts were transplanted with sCD83-only treatment, rapamycin-only treatment, or both agents in combination. While sCD83 monotherapy did not significantly prolong allograft survival and grafts treated with rapamycin monotherapy were rejected with median survival of 16 days, the combination therapy of sCD83 and rapamycin markedly prolonged kidney allograft survival to 30-45 days. The combination therapy further decreased intragraft deposition of IgG, IgM, CD4, CD8 and CD20, all of which are typically associated with heightened immune response, which can negatively impact allograft survival. Additionally, both sCD83 monotherapy and the combination therapy induced a significant increase in circulating T regulatory cells in all recipients.
"This study builds upon our prior studies of sCD83 as a monotherapy and in combination with other therapies and demonstrates that sCD83-based combination therapy may help prolong kidney allograft survival, potentially broadening its therapeutic relevance," said Charles Nicolette, Ph.D., Chief Scientific Officer and Vice President of Research and Development at Argos Therapeutics. "We believe that sCD83 may have significant applications for future clinical development in transplantation and other immune-mediated disorders, particularly considering its favorable safety profile demonstrated thus far with no organ toxicity observed. As such, we are continuing our preclinical development of this program to prepare it for future clinical trials."
Argos also announced that two additional abstracts were accepted for oral presentations at the conference. These abstracts, which were also presented at a prior scientific meeting, are detailed below.
The abstract titled "Modulation of Dendritic Cells by Soluble CD83 Induces Kidney Allograft Tolerance," was selected to receive a Young Investigator Award. According to the abstract, treatment with sCD83 in an animal model of kidney transplantation effectively prevented rejection and achieved long-term graft tolerance, significantly improved survival, and inhibited development of anti-donor antibodies when compared to untreated kidney graft recipients. Additionally, DCs from tolerant sCD83 recipients exhibited significantly decreased expression levels of MHC II, CD40, CD80 and intracellular IL-12, all of which are important to triggering an immune response. These data suggest that sCD83 is multifunctional, and may function via direct mechanisms involving B and T cells and indirectly through DC attenuation.
The third abstract was titled "Soluble CD83 Mediated Suppression of B-cell Activation and Differentiation Prolongs Murine Cardiac Allograft Survival." In a heart transplantation animal model, allograft recipients treated with sCD83 exhibited markedly decreased intragraft B cell infiltration, reduced Immunoglobulins M and G deposition, and significantly lower circulating anti-donor antibody levels. Treatment with sCD83 alone was capable of controlling antibody-mediated rejection and prolonging survival of cardiac allografts by twofold when compared to untreated controls.
The first abstract was authored by ML Baroja, J Arp, Weihua Liu, G Strejan, S Brand, C Nicolette, W Wall, B Garcia, DM Rothstein, AM Jevnikar, and H Wang. The second abstract was authored by: Zhu Lan, Wei Ge, Miren L. Baroja, Jacqueline Arp, Jifu Jiang, Weihua Liu, Stephen Brand, Charles Nicolette, Bertha Garcia and Hao Wang. The third abstract was authored by: Wei Ge, Siobhan I. Ramcharran, Jacqueline Arp, Miren L. Baroja, Zhu Lan, Jifu Jiang, Weihua Liu, Anthony Jevnikar, Stephen Brand, Charles Nicolette, Bertha Gardia and Hao Wang.
About Soluble CD83
CD83 is a glycoprotein expressed on the cell surface of mature dendritic cells (DCs), the most potent stimulators of immune responses. The strong up-regulation of this protein during DC maturation suggests that it plays an important functional role in the induction of immune responses. Experimental data demonstrate that soluble CD83 can potently down-regulate immune responses, indicating that it can be developed to treat transplantation rejection and variety of autoimmune disorders. Importantly, data from animal models demonstrate that soluble CD83 exerts its effects without a requirement for chronic administration and does not leave the subject globally immunosuppressed. The development of CD83 is part of Argos" research and development collaboration with its Canadian partner, DC Bio.
Argos Therapeutics, Inc.