geranyl s thiolodiphosphate gsdp  (Echelon Biosciences)

Journal: iScience

Article Title: Cytosolic bacterial pathogens activate TLR pathways in tumors that synergistically enhance STING agonist cancer therapies

doi: 10.1016/j.isci.2024.111385

Figure Lengend Snippet: Intratumoral delivery of cytosolic bacterial pathogens elicits dose-dependent anti-tumor responses in multiple non-immunogenic murine tumor models (A) Tumor volume (left) and overall survival (right) of mice bearing B16-F10 tumors after intratumoral delivery of 10 7 the indicated strains at d = 0. (B) RMA-bearing C57bl/6j mice were intratumorally injected with PBS or 10 7 Rp sca2 :Tn. (C–E) Tumor volume over time of B16-F10-bearing mice treated with (C) Lm Δ actA Δ inlB ; (D) Bt Δ bimA Δ motA2 ; or (E) Rp sca2 :Tn. Statistics for tumor growth used two-way ANOVA from days 0–20, or if animals were euthanized prior to day 20 the comparisons were made from day 0 up until the final day (day 13 in panels C, D, day 15 in panel E). Statistics for survival used log rank (Mantel-Cox) tests. ∗p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001; ∗∗∗∗ p < 0.0001, ns = not significant. Data for each graph are the combination of at least two separate experiments with a total of at least 8 mice per experimental group. Tumor volume data are means +/- SEM. Tumors were injected on the day that they measured approximately 6 × 6 × 2.5 mm in each direction. Tumor volumes are shown as ellipsoids using the formula: V = (π/6) ABC .

Article Snippet: The anti-tumor effects of bacterial pathogens synergize with the STING agonist S100 (A–I) B16-F10 tumor volume and survival was measured over time after intratumoral delivery with the indicated bacterial species and innate immune agonists. cGAMP (Invivogen) and S100 (Chemietek) were used at 50 μg/mouse and were combined with the bacteria immediately prior to injection.

Techniques: Injection

Journal: iScience

Article Title: Cytosolic bacterial pathogens activate TLR pathways in tumors that synergistically enhance STING agonist cancer therapies

doi: 10.1016/j.isci.2024.111385

Figure Lengend Snippet: Cytosolic access of bacteria promotes the anti-tumor response (A and B) Mice bearing B16-F10 tumors were intratumorally injected with 10 7 of the indicated strains at day 0 and tumor volume and survival were monitored over time. Tumor volume data are means +/- SEM. Statistics for tumor growth used ANOVA at day 10 (A) or day 13 (B) as compared to vehicle PBS; statistics for survival used log rank (Mantel-Cox) tests; ∗p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001; ∗∗∗∗ p < 0.0001; ns = not significant.

Article Snippet: The anti-tumor effects of bacterial pathogens synergize with the STING agonist S100 (A–I) B16-F10 tumor volume and survival was measured over time after intratumoral delivery with the indicated bacterial species and innate immune agonists. cGAMP (Invivogen) and S100 (Chemietek) were used at 50 μg/mouse and were combined with the bacteria immediately prior to injection.

Techniques: Bacteria, Injection

Journal: iScience

Article Title: Cytosolic bacterial pathogens activate TLR pathways in tumors that synergistically enhance STING agonist cancer therapies

doi: 10.1016/j.isci.2024.111385

Figure Lengend Snippet: The microbe-mediated anti-tumor effects are largely independent of cGAS/STING but require TLR signaling (A–J) Tumor-bearing mice were intratumorally administered with 10 7 of bacteria and tumor volume and survival were monitored over time. For (A–E) and (G–J), B16-F10 tumor cells were used, and for (F) B16-BL6 cells were used. For (A–J) Lm was Δ actA Δ inlB and Rp was sca2 :Tn. For (I) 10 μg of TLR2 agonist PAM3CSK4 (Invivogen) was used. Tumor volume data are means +/- SEM. Statistics for tumor growth used two-way ANOVA at day 20 unless otherwise indicated; statistics for survival used log rank (Mantel-Cox) tests. ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001; ∗∗∗∗ p < 0.0001; ns = not significant.

Article Snippet: The anti-tumor effects of bacterial pathogens synergize with the STING agonist S100 (A–I) B16-F10 tumor volume and survival was measured over time after intratumoral delivery with the indicated bacterial species and innate immune agonists. cGAMP (Invivogen) and S100 (Chemietek) were used at 50 μg/mouse and were combined with the bacteria immediately prior to injection.

Techniques: Bacteria

Journal: iScience

Article Title: Cytosolic bacterial pathogens activate TLR pathways in tumors that synergistically enhance STING agonist cancer therapies

doi: 10.1016/j.isci.2024.111385

Figure Lengend Snippet: RAG2 is required for the microbe-mediated anti-tumor effects, while IFNAR or IFNGR are largely dispensable (A–F) B16-F10 tumor bearing mice were intratumorally administered with 10 7 of the indicated bacterial strains and tumor volume and survival were monitored over time. 50 μg of S100 was used, which was combined with the bacteria immediately prior to injection. Tumor volume data are means +/- SEM. Statistics for tumor growth used two-way ANOVA at day 20 unless indicated at an earlier day. Statistics for survival used log rank (Mantel-Cox) tests. Data combined from a minimum of two experiments in which each group had a total minimum of 8 mice. ∗ p < 0.05.

Article Snippet: The anti-tumor effects of bacterial pathogens synergize with the STING agonist S100 (A–I) B16-F10 tumor volume and survival was measured over time after intratumoral delivery with the indicated bacterial species and innate immune agonists. cGAMP (Invivogen) and S100 (Chemietek) were used at 50 μg/mouse and were combined with the bacteria immediately prior to injection.

Techniques: Bacteria, Injection

Journal: iScience

Article Title: Cytosolic bacterial pathogens activate TLR pathways in tumors that synergistically enhance STING agonist cancer therapies

doi: 10.1016/j.isci.2024.111385

Figure Lengend Snippet: The anti-tumor effects of bacterial pathogens synergize with the STING agonist S100 (A–I) B16-F10 tumor volume and survival was measured over time after intratumoral delivery with the indicated bacterial species and innate immune agonists. cGAMP (Invivogen) and S100 (Chemietek) were used at 50 μg/mouse and were combined with the bacteria immediately prior to injection. The strains used were Lm Δ actA Δ inlB ( Lm ), Bt Δ bimA Δ motA2 ( Bt ), or Rp sca2 :Tn ( Rp ). A single injection was performed for all therapies at d = 0. Data are combined from a minimum of two experiments in which each group had a total minimum of 6 mice. Tumor volume data are means +/- SEM. Statistics for tumor growth used ANOVA at day 20 unless otherwise indicated; statistics for survival used log rank (Mantel-Cox) tests. ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001; ∗∗∗∗ p < 0.0001; ns = not significant.

Article Snippet: The anti-tumor effects of bacterial pathogens synergize with the STING agonist S100 (A–I) B16-F10 tumor volume and survival was measured over time after intratumoral delivery with the indicated bacterial species and innate immune agonists. cGAMP (Invivogen) and S100 (Chemietek) were used at 50 μg/mouse and were combined with the bacteria immediately prior to injection.

Techniques: Bacteria, Injection

Journal: iScience

Article Title: Cytosolic bacterial pathogens activate TLR pathways in tumors that synergistically enhance STING agonist cancer therapies

doi: 10.1016/j.isci.2024.111385

Figure Lengend Snippet: IFN-I induction by STING agonists is maintained in infected cells in vitro , and IFNs are not critical for the anti-tumor response in vivo (A) BMDMs were infected with Lm Δ actA Δ inlB ( Lm ), Bt Δ bimA Δ motA2 ( Bt ), or Rp sca2 :Tn ( Rp ) at an MOI of 1. 200 ng of S100 was added immediately after infection and supernatants were collected at 7 hpi. Supernatants were used to stimulate an IFN-I-responsive cell line (ISRE-luciferase) and relative light units (RLUs) were measured 4 h later. Data are combined from ≥3 independent experiments. Data were analyzed using a one-way ANOVA with Tukey’s multiple comparisons test. (B) B16-F10 tumor volume and survival was measured over time after intratumoral delivery with 10 7 Lm Δ actA Δ inlB and 50 μg S100. A single injection was performed for all therapies at d = 0. Data are combined from three independent experiments. Tumor volume data are means +/- SEM. Statistics for tumor growth used two-way ANOVA at day 20; ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001; ∗∗∗∗ p < 0.0001; ns = not significant.

Article Snippet: The anti-tumor effects of bacterial pathogens synergize with the STING agonist S100 (A–I) B16-F10 tumor volume and survival was measured over time after intratumoral delivery with the indicated bacterial species and innate immune agonists. cGAMP (Invivogen) and S100 (Chemietek) were used at 50 μg/mouse and were combined with the bacteria immediately prior to injection.

Techniques: Infection, In Vitro, In Vivo, Luciferase, Injection

Journal: iScience

Article Title: Cytosolic bacterial pathogens activate TLR pathways in tumors that synergistically enhance STING agonist cancer therapies

doi: 10.1016/j.isci.2024.111385

Figure Lengend Snippet: Small molecule STING+TLR agonist combinations elicit synergistic anti-tumor effects (A and B) B16-F10 tumor volume and survival was measured over time. 10 μg of PAM3CSK4 and 50 μg S100 were used per mouse and were injected into palpable tumors. Agonists were combined immediately prior to injection on day 0. Data are combined from two experiments in which each group had a total minimum of 10 mice. Tumor volume data are means +/- SEM. Statistics for tumor growth used two-way ANOVA at day 20; statistics for survival used log rank (Mantel-Cox) tests. ∗ p < 0.05; ∗∗∗∗ p < 0.0001; ns = not significant.

Article Snippet: The anti-tumor effects of bacterial pathogens synergize with the STING agonist S100 (A–I) B16-F10 tumor volume and survival was measured over time after intratumoral delivery with the indicated bacterial species and innate immune agonists. cGAMP (Invivogen) and S100 (Chemietek) were used at 50 μg/mouse and were combined with the bacteria immediately prior to injection.

Techniques: Injection

Journal: iScience

Article Title: Cytosolic bacterial pathogens activate TLR pathways in tumors that synergistically enhance STING agonist cancer therapies

doi: 10.1016/j.isci.2024.111385

Figure Lengend Snippet: Bacterial cancer therapies elicit immunity to tumor cell rechallenge (A and B) Survival of mice after rechallenge with B16-F10 tumors. 10 6 B16-F10 cells were implanted subcutaneously into mice which had previously cleared initial tumors after intratumoral delivery of the indicated therapies. Rechallenges were performed a minimum of 40 days after the primary therapy was delivered. For depletions, antibodies were delivered to tumor bearing mice at days −2, −1, and 0 days prior to tumor rechallenge. Data are combined from a minimum of two experiments in which each group had a total minimum of 8 mice. ∗ p < 0.05; ∗∗ p < 0.01; ∗∗∗ p < 0.001; ∗∗∗∗ p < 0.0001; ns = not significant.

Article Snippet: The anti-tumor effects of bacterial pathogens synergize with the STING agonist S100 (A–I) B16-F10 tumor volume and survival was measured over time after intratumoral delivery with the indicated bacterial species and innate immune agonists. cGAMP (Invivogen) and S100 (Chemietek) were used at 50 μg/mouse and were combined with the bacteria immediately prior to injection.

Techniques:

Journal: iScience

Article Title: Cytosolic bacterial pathogens activate TLR pathways in tumors that synergistically enhance STING agonist cancer therapies

doi: 10.1016/j.isci.2024.111385

Figure Lengend Snippet:

Article Snippet: The anti-tumor effects of bacterial pathogens synergize with the STING agonist S100 (A–I) B16-F10 tumor volume and survival was measured over time after intratumoral delivery with the indicated bacterial species and innate immune agonists. cGAMP (Invivogen) and S100 (Chemietek) were used at 50 μg/mouse and were combined with the bacteria immediately prior to injection.

Techniques: Control, Virus, Recombinant, Mouse Assay, Mutagenesis, Software

Journal: Journal of Clinical Medicine

Article Title: Challenges and Opportunities in the Clinical Development of STING Agonists for Cancer Immunotherapy

doi: 10.3390/jcm9103323

Figure Lengend Snippet: STING Agonists in Clinical Trials.

Article Snippet: ADU-S100 (i.t.) + PDR001(i.v.) (spartalizumab) , Novartis , Solid tumours; lymphomas , Ib , 09/17 , Terminated 12/19 , Data cut-off: 5th April 2019 - 12/53 SD, 4/53 PR, 1/53 CR - Responders: median reduction of 73% in 1° lesion diameter - 78% TRAEs, 12.2% of TRAEs = grade3/4 - No DLTs - MTD not determined - T1/2 = 10–23 min , NCT03172936.

Techniques:

Journal: Journal of Clinical Medicine

Article Title: Challenges and Opportunities in the Clinical Development of STING Agonists for Cancer Immunotherapy

doi: 10.3390/jcm9103323

Figure Lengend Snippet: STING agonist drug delivery systems for cancer immunotherapies.

Article Snippet: ADU-S100 (i.t.) + PDR001(i.v.) (spartalizumab) , Novartis , Solid tumours; lymphomas , Ib , 09/17 , Terminated 12/19 , Data cut-off: 5th April 2019 - 12/53 SD, 4/53 PR, 1/53 CR - Responders: median reduction of 73% in 1° lesion diameter - 78% TRAEs, 12.2% of TRAEs = grade3/4 - No DLTs - MTD not determined - T1/2 = 10–23 min , NCT03172936.

Techniques: