LF 15-0195 (LF) is a new analogue of 15-deoxyspergualin (DSG) that is less toxic and more potent than DSG. The present study was undertaken to determine (1). the dose response of LF monotherapy, (2). its ability to induce tolerance, and (3) its interaction with cyclosporine (CsA), FK 506 (FK), and rapamycin (RAPA). Varying doses of LF were administered to determine dose-dependent effects on graft survival in a C57BL/6 to BALB/c heterotopic heart allograft mouse model. Transplanting-donor and third-party skin grafts into long-term survivors were used to assess the tolerance status. CsA, FK, and RAPA were combined with LF to determine their interactive effects on graft survival. The efficacy and toxicity of LF was dose dependent. High-dose LF monotherapy (>2 mg/kg) induced donor-specific operational tolerance, but it was associated with high mortality. Simultaneous administration of high-dose calcineurin inhibitors (CsA FK) prevented tolerance induced by LF. In contrast, a short course of LF combined with a subtherapeutic dose of CsA FK achieved indefinite survival of C57/BL6 cardiac allografts. RAPA and LF had a synergistic effect in induction of tolerance. The efficacy and toxicity of LF were dose dependent. A short course of L...Continue Reading
A novel rescue drug, 15-deoxyspergualin. First clinical trials for recurrent graft rejection in renal recipients
Effect of the new immunosuppressive agent, cyclosporin-A, on natural killer cell and antibody-dependent cell-mediated cytotoxic activity
Structure-immunosuppressive activity relationships of new analogues of 15-deoxyspergualin. 1. Structural modifications of the hydroxyglycine moiety
Cyclosporine inhibits long-term survival in cardiac allografts treated with monoclonal antibody against CD45RB
Blocking both signal 1 and signal 2 of T-cell activation prevents apoptosis of alloreactive T cells and induction of peripheral allograft tolerance
Deoxyspergualin delays xenograft rejection in the guinea pig-to-C6-deficient rat heart transplantation model
Role for thymic and splenic regulatory CD4+ T cells induced by donor dendritic cells in allograft tolerance by LF15-0195 treatment
LF 15-0195 prevents from the development and inhibits the progression of rat experimental autoimmune myasthenia gravis
LF 15-0195 immunosuppressive agent enhances activation-induced T-cell death by facilitating caspase-8 and caspase-10 activation at the DISC level.
Monotherapy with LF 15-0195, an analogue of 15-deoxyspergualin, significantly prolongs renal allograft survival in monkeys
Attenuation of acute xenograft rejection by short-term treatment with LF15-0195 and monoclonal antibody against CD45RB in a rat-to-mouse cardiac transplantation model
Rapamycin does not induce anergy but inhibits expansion and differentiation of alloreactive human T cells
Control of cyclosporine A-induced tumor progression using 15-deoxyspergualin for rat cardiac transplantation
Long-term limb allograft survival using a short course of anti-CD45RB monoclonal antibody, LF 15-0195, and rapamycin in a mouse model
Preventing autoimmune arthritis using antigen-specific immature dendritic cells: a novel tolerogenic vaccine
Is there B cell involvement in a rat model of spontaneous idiopathic nephrotic syndrome treated with LF15-0195?
Differential promotion of hematopoietic chimerism and inhibition of alloreactive T cell proliferation by combinations of anti-CD40Ligand, anti-LFA-1, everolimus, and deoxyspergualin
Generation of therapeutic dendritic cells and regulatory T cells for preventing allogeneic cardiac graft rejection
C5 blockade with conventional immunosuppression induces long-term graft survival in presensitized recipients
Induction of chimerism in rhesus macaques through stem cell transplant and costimulation blockade-based immunosuppression
Regulatory B Cells with a Partial Defect in CD40 Signaling and Overexpressing Granzyme B Transfer Allograft Tolerance in Rodents
Treatment with a short course of LF 15-0195 and continuous cyclosporin A attenuates acute xenograft rejection in a rat-to-mouse cardiac transplantation model
LF 15-0195 treatment protects against central nervous system autoimmunity by favoring the development of Foxp3-expressing regulatory CD4 T cells
Combining autologous dendritic cell therapy with CD3 antibodies promotes regulatory T cells and permanent islet allograft acceptance
Preventing alloimmune rejection using circular RNA FSCN1-silenced dendritic cells in heart transplantation.
Allogenic & Autologous Therapies
Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.