indoximod 1-methyl-d-tryptophan 1mt nlg-8189  (NewLink Genetics)

Journal: Regenerative Biomaterials

Article Title: A lipid/PLGA nanocomplex to reshape tumor immune microenvironment for colon cancer therapy

doi: 10.1093/rb/rbae036

Figure Lengend Snippet: TEM images of CM ( A ), RCM ( B ) and RDCM ( C ); scale bars represent 50 nm. DLS sizes of blank CM, RCM and RDCM ( D ). The release curves of Ce6 ( E ) and 1MT ( F ) in vitro . Cell viability of CT26 cells incubated with 1MT, CM-1, RCM-1 and RDCM-1 ( G ), Ce6 + 1MT, CM, RCM and RDCM for 48 h ( H ). Cell viability of CT26 cells incubated with Ce6 + 1MT, CM, RCM and RDCM for 24 h after 660 nm laser irradiation for 30 s ( I ) ( n = 3, * P < 0.05, ** P < 0.01).

Article Snippet: 1-Methyl-D-tryptophan (1MT) was obtained from Selleck (Shanghai, China).

Techniques: In Vitro, Incubation, Irradiation

Journal: Regenerative Biomaterials

Article Title: A lipid/PLGA nanocomplex to reshape tumor immune microenvironment for colon cancer therapy

doi: 10.1093/rb/rbae036

Figure Lengend Snippet: CLSM images and FCM results of cellular uptake ( A , C and D ) and intracellular ROS ( B , E and F ) ( n = 3, * P < 0.05, ** P < 0.01). Apoptosis rates of cells treated with Ce6 + 1MT, CM, RCM and RDCM after 660 nm laser irradiation ( G ).

Article Snippet: 1-Methyl-D-tryptophan (1MT) was obtained from Selleck (Shanghai, China).

Techniques: Irradiation

Journal: Regenerative Biomaterials

Article Title: A lipid/PLGA nanocomplex to reshape tumor immune microenvironment for colon cancer therapy

doi: 10.1093/rb/rbae036

Figure Lengend Snippet: CLSM images and semi-quantitative of CRT ( A , C ) and HMGB1 ( B , D ) of CT26 cells treated with Ce6 + 1MT, CM, RCM and RDCM after 660 nm laser irradiation. ATP released from CT26 cells treated with Ce6 + 1MT, CM, RCM and RDCM after 660 nm laser irradiation ( E ). Affinity detection of RDCM to PD-L1 after pretreatment with MMP-2 ( F and G ). Kyn inhibition rates of CT26 cells ( H ). n = 3, * P < 0.05, ** P < 0.01.

Article Snippet: 1-Methyl-D-tryptophan (1MT) was obtained from Selleck (Shanghai, China).

Techniques: Irradiation, Inhibition

Journal: Journal for Immunotherapy of Cancer

Article Title: The indoleamine 2,3-dioxygenase pathway controls complement-dependent enhancement of chemo-radiation therapy against murine glioblastoma

doi: 10.1186/2051-1426-2-21

Figure Lengend Snippet: IDO-blockade synergizes with chemo-radiation therapy. Orthotopic GL261 glioblastoma tumors were implanted stereotactically into the right frontal lobes of syngeneic C57BL/6 host mice. Kaplan-Meier survival plots are shown, comparing mice treated with: A , temozolomide plus radiation (TMZ + RT) and with or without IDO-blockade using DL-1MT; B , TMZ + RT and with or without IDO-blockade using NLG919 or D-1MT; C , cyclophosphamide plus RT (CPM + RT) and with or without DL-1MT; or D , with CPM + RT plus either D-1MT or DL-1MT. IDO-blocking drugs (DL-1MT, 4 mg/mL; NLG919, 6 mg/mL; or D-1MT, 4 mg/mL) were supplied in drinking water continuously starting at day 7 after tumor implantation; chemotherapy (TMZ, 100 mg/kg, i.p.; or CPM, 100 mg/kg, i.p.) was given on day 9, and RT (500 cGy) was given on day 10. For reference, each survival plot contains a cohort of untreated mice, and mice treated with IDO-blockade using DL-1MT alone are shown in A . Cohort sizes (n) are indicated for each treatment group and represent pooled data from multiple experiments containing 1–3 mice from each group per experiment. n.s., not significant [vs. untreated mice (A) ; or DL-1MT vs. D-1MT (D) ]; *, P < 0.001 (vs. untreated mice); **, P < 0.002 (vs. mice treated with chemo-radiation alone), by log-rank test.

Article Snippet: IDO-inhibitor drugs 1-methyl-D-tryptophan (D-1MT, catalog no. 452483) and 1-methyl-L-tryptophan (L-1MT, catalog no. 447439) were purchased from Sigma-Aldrich, and NLG919 was a generous gift from Mario Mautino (NewLink Genetics).

Techniques: Blocking Assay, Tumor Implantation

Journal: Journal for Immunotherapy of Cancer

Article Title: The indoleamine 2,3-dioxygenase pathway controls complement-dependent enhancement of chemo-radiation therapy against murine glioblastoma

doi: 10.1186/2051-1426-2-21

Figure Lengend Snippet: IDO-blockade drives vascular activation after chemotherapy and tumor necrosis after chemo-radiation therapy. A , GL261 tumors were grown in WT host mice treated with TMZ (100 mg/kg, i.p.) and with or without IDO-blockade using 1MT (4 mg/mL in drinking water). Tumors were harvested 5 days after chemotherapy (18 days after implantation) and frozen for immunohistochemical analysis of vascular cell adhesion molecule-1 (VCAM-1, red) on endothelial cells (CD31, green). Nuclei were counterstained with Hoechst (blue). Representative photomicrographs are shown of at least 3 mice per group, from at least 3 independent experiments. Original magnification, ×400; Scale bars, 25 μm. B , GL261 tumors were grown in WT host mice treated with TMZ (100 mg/kg, i.p.) + RT (500 cGy) and with or without 1MT (4 mg/mL in drinking water). Tumors were harvested in formalin 5 days after chemotherapy and stained with hematoxylin and eosin for assessment of tissue architecture. Call-out panel highlights an area of local tumor necrosis. Data are representative of at least 3 mice per group, from at least 3 independent experiments. Original magnification, ×200 (upper panels) and ×400 (lower call-out panel); Scale bars, 25 μm.

Article Snippet: IDO-inhibitor drugs 1-methyl-D-tryptophan (D-1MT, catalog no. 452483) and 1-methyl-L-tryptophan (L-1MT, catalog no. 447439) were purchased from Sigma-Aldrich, and NLG919 was a generous gift from Mario Mautino (NewLink Genetics).

Techniques: Activation Assay, Immunohistochemical staining, Staining

Journal: Journal for Immunotherapy of Cancer

Article Title: The indoleamine 2,3-dioxygenase pathway controls complement-dependent enhancement of chemo-radiation therapy against murine glioblastoma

doi: 10.1186/2051-1426-2-21

Figure Lengend Snippet: Inhibition or absence of IDO triggers widespread complement deposition in tumors after chemo-radiation therapy. GL261 tumors were grown in syngeneic host mice treated with or without IDO-blocking drugs (1MT, 4 mg/mL; or NLG919, 6 mg/mL) in drinking water starting on day 14, plus TMZ (100 mg/kg, i.p.) on day 16 and RT (500 cGy) on day 17. Tumors were harvested on day 18 and frozen for immunohistochemical analysis of complement component C3 deposition (red) endothelial cells (CD31, green), and nuclei (Hoechst, blue). A , representative photomicrographs of control tumors from WT host mice, either untreated or treated with TMZ + RT. B , representative photomicrographs of tumors and adjacent normal brain from WT host mice treated with either TMZ + RT + 1MT or TMZ + RT + NLG919; and from syngeneic IDO-deficient host mice treated with TMZ + RT. Data are representative of at least 3 mice per group, from at least 3 independent experiments. Original magnification, ×400; Scale bars, 25 μm. C to E , quantitative analysis of complement deposition. Photomicrographs of tumors stained for complement C3 (red) were obtained in a grid pattern at magnification ×400, and image analysis software was used to abstract fluorescence intensity histograms from each photomicrograph for quantitative analysis. C , Representative photomicrographs and histograms are shown. Scale bars, 25 μm. Histograms are labeled with mean fluorescence intensity (MFI) and the proportion of pixels occurring downfield from an arbitrarily-chosen negative threshold (channel thirty-two). Comparisons of MFI (D) and Percent Downfield Pixels (E) are shown with means represented by a solid bar. For each experimental group, at least 35 photomicrographs were analyzed from 3 separate mice pooled from 3 independent experiments. *, P < 0.02; **, P < 0.002; ***, P < 10 -6 (vs. WT mice treated with TMZ + RT), by ANOVA with Kruskal-Wallis test.

Article Snippet: IDO-inhibitor drugs 1-methyl-D-tryptophan (D-1MT, catalog no. 452483) and 1-methyl-L-tryptophan (L-1MT, catalog no. 447439) were purchased from Sigma-Aldrich, and NLG919 was a generous gift from Mario Mautino (NewLink Genetics).

Techniques: Inhibition, Blocking Assay, Immunohistochemical staining, Staining, Software, Fluorescence, Labeling

Journal: Journal for Immunotherapy of Cancer

Article Title: The indoleamine 2,3-dioxygenase pathway controls complement-dependent enhancement of chemo-radiation therapy against murine glioblastoma

doi: 10.1186/2051-1426-2-21

Figure Lengend Snippet: Complement is mechanistically required for IDO-blockade to synergize with chemo-radiation therapy. GL261 tumors were grown in syngeneic WT (upper panel) or complement C3-deficient (lower panel) host mice. Kaplan-Meier survival plots are shown, comparing mice treated with: A , temozolomide plus radiation (TMZ + RT) and with or without IDO-blockade using DL-1MT; or B, cyclophosphamide plus radiation (CPM + RT) and with or without DL-1MT. DL-1MT (4 mg/mL) was supplied in drinking water continuously starting at day 7 after tumor implantation; chemotherapy (TMZ, 100 mg/kg; or CPM, 100 mg/kg) was given on day 9, and RT (500 cGy) was given on day 10. For reference, each survival plot contains a cohort of untreated host mice. Cohort sizes (n) are indicated for each treatment group and represent pooled data from multiple experiments containing 1–3 mice from each group per experiment. *, P < 0.0001 (vs. mice treated with chemo-radiation alone); n.s., not significant (vs. mice treated with chemo-radiation alone), by log-rank test.

Article Snippet: IDO-inhibitor drugs 1-methyl-D-tryptophan (D-1MT, catalog no. 452483) and 1-methyl-L-tryptophan (L-1MT, catalog no. 447439) were purchased from Sigma-Aldrich, and NLG919 was a generous gift from Mario Mautino (NewLink Genetics).

Techniques: Tumor Implantation

Journal: PLoS ONE

Article Title: HIV-Induced Type I Interferon and Tryptophan Catabolism Drive T Cell Dysfunction Despite Phenotypic Activation

doi: 10.1371/journal.pone.0002961

Figure Lengend Snippet: CFSE-labeled PBMC from HIV-uninfected donor were cultured for 24 hours in presence of control microvescicles, HIV alone, or in presence of the IDO inhibitor 1-methyl-D-tryptophan (1mT). After 24 hours anti-CD3 was added to the cultures and cells were analyzed by flow cytometry after 72 hours. (A) Flow cytometry histograms showing CFSE dilution for one example experiment for CD4 (left panels) and CD8 T cells (right panels) are shown. Upper panels show the comparison between control-pretreated cells (green line) and HIV-pretreared cells (red line); bottom panels show the comparison between HIV-pretreared cells (red line) and cells pretreated with HIV in presence of 1mT (Blue line). One representative of 5 independent experiments is shown. (B) Bar graphs showing division index (number of cell divisions/total cell number) and proliferation index (number of cell divisions/number of divided cells) of CD4 (left panels) and CD8 T cells (right panels) pretreated with AT-2 HIV or mock and stimulated with anti-CD3 in presence (solid bars) or absence (open bars) of 1mT. Mean values±standard error calculated on 5 independent experiments are shown.

Article Snippet: CFSE-labeled PBMC from five different donors were cultured in presence or absence of AT-2 HIV as described above, with or without 1-methyl-D-tryptophan (1mT, 200 µM) (Sigma).

Techniques: Labeling, Cell Culture, Flow Cytometry