The research program of ITBMed is directed toward the development of products that will improve the quality of life of transplant patients by bringing transplantation tolerance to the clinic. The first product being developed is Siplizumab, a recombinant monoclonal antibody directed toward the human CD2 cell-surface molecule, expressed on T cells and NK cells (1). This monoclonal antibody has unique immunomodulatory properties, due to its ability to effect both T cell depletion and co-stimulatory blockade, the latter of which most likely results through its unique mode of interaction with its ligand, LFA-3, on antigen-presenting cells. Initial clinical studies have demonstrated the ability of this antibody to enable the induction of transplantation tolerance in a series of patients receiving kidney transplants across major HLA histocompatibility barriers (2-4). Some of these patients have already achieved stable renal function for over 10 years without immunosuppressive drugs.
The quality of life of these patients is demonstrably improved over patients with stable renal function who are still required to take immunosuppessive medications (5). ITBMed is studying the mechanism of action of Siplizumab and its ability to facilitate the induction of tolerance in additional transplant settings.
As part of the preclinical research and development profile ITBMed have a collaboration with Columbia University, New York, USA, that has the potential to provide novel IP and break ground for new indications and treatments.
- Xu, Y., D. Kolber-Simonds, J.A. Hope, H. Bazin, D. Latinne, R. Monroy, M.E. White-Scharf, and H.J. Schuurman. 2004. The anti-CD2 monoclonal antibody BTI-322 generates unresponsiveness by activation-associated T cell depletion. Clin. Exp. Immunol. 138:476-483.
- Kawai, T., A.B. Cosimi, T.R. Spitzer, N. Tolkoff-Rubin, M. Suthanthiran, S.L. Saidman, J. Shaffer, F.I. Preffer, et al. 2008. HLA-mismatched renal transplantation without maintenance immunosuppression. N. Engl. J. Med. 358:353-361.
- Kawai, T., D.H. Sachs, B. Sprangers, T.R. Spitzer, S.L. Saidman, E. Zorn, N. Tolkoff-Rubin, F. Preffer, et al. 2014. Long-term results in recipients of combined HLA-mismatched kidney and bone marrow transplantation without maintenance immunosuppression. Am. J. Transplant. 14:1599-1611.
- Kawai, T., D.H. Sachs, M. Sykes, and A.B. Cosimi. 2013. HLA-mismatched renal transplantation without maintenance immunosuppression. N. Engl. J. Med. 368:1850-1852.
- Madariaga, M.L., P.J. Spencer, K. Shanmugarajah, K.A. Crisalli, D.C. Chang, J.F. Markmann, N. Elias, A.B. Cosimi, et al. 2016. Effect of tolerance versus chronic immunosuppression protocols on the quality of life of kidney transplant recipients. JCI Insight. 2;1(8).