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[求助]
求各位帮忙翻译一下如下医学英语
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NewLink presented preclinical data related to the immunostimulatory and anti-tumor effects of its two clinical-stage checkpoint inhibitors targeting the IDO pathway, indoximod and NLG919, in combination with anti-PD-1/PD-L antibodies. In a poster presentation entitled "Synergistic antitumor effects of combinatorial immune checkpoint inhibition with anti-PD-1/PD-L antibodies and the IDO pathway inhibitors NLG-919 and indoximod in the context of active immunotherapy" NewLink researchers and collaborators at Georgia Regents University presented preclinical data demonstrating that combining IDO pathway inhibitors with agents targeting immune checkpoints provided enhanced anti-tumor effect compared to either agent alone in mouse models of established tumors. The presentation took place at the American Association for Cancer Research (AACR) 2014 Annual Meeting on April 9, 2014. Context NewLink Genetics has tested the antitumor effect of the IDO pathway inhibitor NLG-919 (currently in Phase I clinical trial) in combination with indoximod (a different IDO pathway inhibitor currently in Phase II clinical trials), chemotherapy, vaccination and/or PD-1/PD-L1/PD-L2 blockade. Design Here the Company showed that the highly potent, orally-bioavailable IDO pathway inhibitor NLG-919 is synergistic with blockade of the PD-1/PD-L1/PD-L2 pathway in mouse models of large established tumors. Results Results demonstrated synergistic effects of combining NLG919, indoximod and anti-PD-1/PD-L1/PD-L2 antibodies to block both the IDO and PD pathways resulting in enhanced anti-tumor effects compared to blocking each pathway independently. This synergy was demonstrated in the context of established tumors treated with otherwise ineffective chemo-immunotherapy regimens. Per the abstract, the combination of NLG-919 plus PD-1/PD-L1/PD-L2 blockade showed significantly enhanced anti-tumor effect compared to either agent alone. This synergy was particularly evident in the setting of large established tumors treated with normally ineffective immunotherapy regimens (e.g., a single dose of chemotherapy plus a vaccine against a poorly immunogenic shared-self antigen). In vivo, administration of NLG-919 enhanced anti-tumor vaccine responses against B16F10 melanoma treated with hgp100 vaccine plus resting, non-activated pmel-1 T cells NLG-919 also reduced Treg-mediated suppression in tumor-bearing hosts, and enhanced dendritic cell activation in tumors and TDLNs. In combination with chemotherapy, treatment with NLG-919 allowed effector T cell responses against endogenous tumor antigens released by chemotherapy. By each of the preceding readouts, the in vivo biologic effect of NLG-919 was qualitatively identical to that of indoximod, but the same immunologic effects could be achieved at lower plasma concentrations in vivo. In a more stringent B16F10 melanoma tumor model that did not involve adoptive transfer of pmel-1 cells, a combination of immune checkpoint inhibition involving NLG-919, indoximod and anti-PD1/PD-L1/PD-L2 antibodies with chemotherapy and hgp100 peptide vaccine was able to achieve a significant antitumor effect. |
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