Disease relevance of LF 15-0195

• LF 15-0195 prevents from the development and inhibits the progression of rat experimental autoimmune myasthenia gravis [1].
• These finding suggest that LF 15-0195 is a promising therapeutic for this autoimmune disease [1].
• OBJECTIVES: LF 15-0195 is an immunosuppressive agent obtained by organic synthesis, currently under clinical development for the treatment of vasculitis [2].
• Beneficial effect of the immunosuppressant LF 15-0195 on passively induced rat experimental autoimmune encephalomyelitis [3].

High impact information on LF 15-0195

• In these cells, LF 15-0195 increased apoptosis triggered by either anti-CD95 antibodies or CD3 restimulation, whereas no effect was observed on "passive apoptosis." Finally, in bone marrow recipient mice, LF 15-0195 enhanced allogeneic donor T-cell death, which required a functional CD95 pathway [4].
• LF 15-0195 immunosuppressive agent enhances activation-induced T-cell death by facilitating caspase-8 and caspase-10 activation at the DISC level [4].
• LF 15-0195 also sensitizes Jurkat T cells to CD3-mediated apoptosis, an in vitro model for activation-induced T-cell death (AICD) [4].
• These results suggest that LF 15-0195 sensitizes T cells to AICD by increasing caspase activation at the DISC level in response to CD95 engagement [4].
• We show that exposure to LF 15-0195 sensitizes Jurkat T cells to apoptosis induced by an agonistic anti-CD95 antibody (CH11 clone) and by the cytokine TNF-related apoptosis-inducing ligand [4].

Biological context of LF 15-0195

• LF 15-0195 inhibits the development of rat central nervous system autoimmunity by inducing long-lasting tolerance in autoreactive CD4 T cells [5].
• LF 15-0195 treatment significantly prolonged graft survival in groups 2, 3, and 4, to 20+/-20 days, 49+/-5 days, and 39+/-4 days, respectively [6].
• Pathologic studies demonstrated that vascular graft rejection was attenuated in LF 15-0195-treated allografts, compared with control specimens [6].
• Sequential studies on days 6 and 14 demonstrated that LF 15-0195 either alone or combined with CsA completely inhibited antibody production [7].
• The immunosuppressant LF 15-0195 prevents collagen-induced arthritis with IL-10 down-regulation [8].

Anatomical context of LF 15-0195

• This drug also inhibits ongoing and passively induced EAE, indicating that LF 15-0195 affects already differentiated pathogenic lymphocytes [5].
• Compared with lymph node cells from untreated rats, lymphocytes from MBP-immunized rats treated with LF 15-0195 proliferated equally well in response to MBP in vitro, while their ability to produce effector cytokines and to transfer EAE into syngeneic recipients was significantly reduced [5].
• LF 15-0195 did not significantly alter thrombocyte counts or hemoglobin levels [6].
• BACKGROUND: LF 15-0195 (LF), a novel analogue of 15-deoxyspergualin (DSG), inhibits maturation of dendritic cells (DC) [9].
• However, intragraft infiltration by Mac-1 positive cells including natural killer cells, macrophages and granulocytes in LF 15-0195 treated recipients was similar to that of untreated recipients [7].

Associations of LF 15-0195 with other chemical compounds

• Monotherapy with LF 15-0195, an analogue of 15-deoxyspergualin, significantly prolongs renal allograft survival in monkeys [6].
• 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 [7].

Gene context of LF 15-0195

• LF 15-0195-mediated sensitization to AICD was further confirmed in human peripheral T cells exposed to anti-CD3 antibodies, then cultured in the presence of interleukin-2 [4].
• We show that LF 15-0195 administration at the time of MBP immunization reduces the incidence and severity of EAE in Lewis rats [5].
• Together, these data demonstrate that short-term treatment with LF 15-0195 prevents MBP-immunized LEW rats from EAE by favoring the development of Foxp-3-expressing regulatory CD4 T cells [10].
• Finally, we demonstrate that the tolerance induced by LF 15-0195 treatment is not dependent on the presence of TGF-beta [10].
• LF 15-0195 inhibited B cell differentiation with a marked suppression of anti-CII IgG1 and IgG2a synthesis [2].

Analytical, diagnostic and therapeutic context of LF 15-0195

• CONCLUSIONS: LF 15-0195 monotherapy significantly prolonged renal allograft survival in monkeys [6].
• Here we investigated whether immune response could be prevented by treatment with compounds known to induce tolerance in organ transplantation: CTLA4Ig and LF-15-0195 [11].
• LF-15-0195 was administered i.p. All animals were subjected to partial hepatectomy and received beta-galactosidase retroviral vectors intravenously [11].
• Longterm protection of mice against collagen-induced arthritis after short-term LF 15-0195 treatment: modulation of B and T lymphocyte activation [2].
• The present study was undertaken to determine the efficacy of LF 15-0195, a new immunosuppressive analog of 15-deoxyspergualin in the prevention of AVR in a rat-to-mouse cardiac xenograft model [7].

References