Journal: Cancers

Article Title: Semi-Mechanistic Model for the Antitumor Response of a Combination Cocktail of Immuno-Modulators in Non-Inflamed (Cold) Tumors

doi: 10.3390/cancers13205049

Figure Lengend Snippet: Summary of study design characteristics.

Article Snippet: When the average tumor diameter reached 5 mm, mice were randomly divided into groups receiving treatments consisting of mono-, bi-, or triple-therapy based on an E7 long peptide (Antigen (Ag)), a TLR-3 agonist (polyinosinic-polycytidylic acid (PIC)) (ThermoFisher; Massachusetts MA, USA), and an anti-PD1 (αPD1) (CD279; clone RMP1-14; BioXCell; New Hampshire NH, USA). shows the different treatment groups with the corresponding number of mice.

Techniques: Control

Journal: Cancers

Article Title: Semi-Mechanistic Model for the Antitumor Response of a Combination Cocktail of Immuno-Modulators in Non-Inflamed (Cold) Tumors

doi: 10.3390/cancers13205049

Figure Lengend Snippet: Overview of the biological processes considered by the model, together with the different model assumptions and the experimental data supporting those processes.

Article Snippet: When the average tumor diameter reached 5 mm, mice were randomly divided into groups receiving treatments consisting of mono-, bi-, or triple-therapy based on an E7 long peptide (Antigen (Ag)), a TLR-3 agonist (polyinosinic-polycytidylic acid (PIC)) (ThermoFisher; Massachusetts MA, USA), and an anti-PD1 (αPD1) (CD279; clone RMP1-14; BioXCell; New Hampshire NH, USA). shows the different treatment groups with the corresponding number of mice.

Techniques: Control, Clinical Proteomics, Activation Assay, Expressing

Journal: Cancers

Article Title: Semi-Mechanistic Model for the Antitumor Response of a Combination Cocktail of Immuno-Modulators in Non-Inflamed (Cold) Tumors

doi: 10.3390/cancers13205049

Figure Lengend Snippet: Schematic representation of the immuno-oncology therapy model, including the interactions of immune cells with cancer cells after the administration of antigen Ag, PIC, and αPD1. Dashed green arrows indicate activation, dashed red blocked arrows indicate inhibition, dashed yellow arrows indicate the effect of PIC, and solid sharped arrows indicate the transit between compartments. TRT and TR denote treatment and transit compartments, respectively. APC stands for antigen-presenting cells, and RES for the resistance mechanisms developed by the tumor. A description of the parameters can be found in Material and Methods.

Article Snippet: When the average tumor diameter reached 5 mm, mice were randomly divided into groups receiving treatments consisting of mono-, bi-, or triple-therapy based on an E7 long peptide (Antigen (Ag)), a TLR-3 agonist (polyinosinic-polycytidylic acid (PIC)) (ThermoFisher; Massachusetts MA, USA), and an anti-PD1 (αPD1) (CD279; clone RMP1-14; BioXCell; New Hampshire NH, USA). shows the different treatment groups with the corresponding number of mice.

Techniques: Activation Assay, Inhibition

Journal: Cancers

Article Title: Semi-Mechanistic Model for the Antitumor Response of a Combination Cocktail of Immuno-Modulators in Non-Inflamed (Cold) Tumors

doi: 10.3390/cancers13205049

Figure Lengend Snippet: The typical model-predicted profiles of activated CD8 cells ( A ) and tumor size (TS) ( B ) over time, corresponding to the different treatment groups: antigen monotherapy for responder (dark green) and non-responder mice (light green), Ag and PIC treated as monotherapy (dark blue) and as bi-therapy (light blue), and Ag and αPD1 (red). Arrows indicate the day of dosing time for antigen (green), PIC (blue), and αPD1 (red).

Article Snippet: When the average tumor diameter reached 5 mm, mice were randomly divided into groups receiving treatments consisting of mono-, bi-, or triple-therapy based on an E7 long peptide (Antigen (Ag)), a TLR-3 agonist (polyinosinic-polycytidylic acid (PIC)) (ThermoFisher; Massachusetts MA, USA), and an anti-PD1 (αPD1) (CD279; clone RMP1-14; BioXCell; New Hampshire NH, USA). shows the different treatment groups with the corresponding number of mice.

Techniques:

Journal: Cancers

Article Title: Semi-Mechanistic Model for the Antitumor Response of a Combination Cocktail of Immuno-Modulators in Non-Inflamed (Cold) Tumors

doi: 10.3390/cancers13205049

Figure Lengend Snippet: Model parameter estimates.

Article Snippet: When the average tumor diameter reached 5 mm, mice were randomly divided into groups receiving treatments consisting of mono-, bi-, or triple-therapy based on an E7 long peptide (Antigen (Ag)), a TLR-3 agonist (polyinosinic-polycytidylic acid (PIC)) (ThermoFisher; Massachusetts MA, USA), and an anti-PD1 (αPD1) (CD279; clone RMP1-14; BioXCell; New Hampshire NH, USA). shows the different treatment groups with the corresponding number of mice.

Techniques:

Journal: Cancers

Article Title: Semi-Mechanistic Model for the Antitumor Response of a Combination Cocktail of Immuno-Modulators in Non-Inflamed (Cold) Tumors

doi: 10.3390/cancers13205049

Figure Lengend Snippet: Effect of the area under the levels of activated CD8 ( A – D ) and resistance inhibition induced by αPD1 ( E , F ) vs. time curve (AUC CD8 and AUC resistance_inhibition , respectively) on response rates expressed as a percentage of mice showing total response (red), transient response (blue), and absence of response (green). One thousand animals for each of the 100 different parameter combinations were simulated for the multiple treatment groups: ( A ) Ag, ( B ) Ag and PIC, ( C , E ) Ag and αPD1, and ( D , F ) triple-therapy.

Article Snippet: When the average tumor diameter reached 5 mm, mice were randomly divided into groups receiving treatments consisting of mono-, bi-, or triple-therapy based on an E7 long peptide (Antigen (Ag)), a TLR-3 agonist (polyinosinic-polycytidylic acid (PIC)) (ThermoFisher; Massachusetts MA, USA), and an anti-PD1 (αPD1) (CD279; clone RMP1-14; BioXCell; New Hampshire NH, USA). shows the different treatment groups with the corresponding number of mice.

Techniques: Inhibition

Journal: Biomarker Research

Article Title: Targeting TIGIT for cancer immunotherapy: recent advances and future directions

doi: 10.1186/s40364-023-00543-z

Figure Lengend Snippet: Selected Preclinical studies of anti-TIGIT agents in solid and hematological tumors

Article Snippet: , VV- scFv- TIGIT b [ ] , 200 μg (anti-PD-1) i.p. every 2 days for 6–7 doses 200 μg (anti-LAG-3) i.p. every 4 days for 3 doses , CT26, MC38,4 T1, H22 bearing BALB/c or C57BL/6 mouse model , The intratumoral injection of VV-scFv-TIGIT elicited anti-tumor function, prolonged survival, increased T cells infiltration and activation of CD8 + T cells. Combination of anti-PD-1 or anti-LAG-3 enhanced the anti-tumor efficacy. , Anti-PD-1 (αPD1, Clone RMP1–14, Cat# BE0146, BioXCell) Anti-LAG3 (αLAG- 3, Clone C9B7W, Cat# BE0174, BioXCell) , Colorectal Carcinoma Breast Cancer Hepatocellular Carcinoma.

Techniques: Knock-In, Cell Function Assay, Injection, Activation Assay, Amplification, Control, Incubation, Lysis

Journal: JCI Insight

Article Title: Priming is key to effective incorporation of image-guided thermal ablation into immunotherapy protocols

doi: 10.1172/jci.insight.90521

Figure Lengend Snippet: (A) Regimen of coincident TA-immunotherapy, CpG (100 μg per injection, intratumoral [i.t.]) and anti–PD-1 (αPD-1) (200 μg per injection, i.p.) in mice orthotopically transplanted with NDL tumor biopsies in the fourth and ninth mammary fat pad. (B and C) Tumor growth was followed until an animal from the group was euthanized (tumor diameter >1.5 cm). Treatment cohorts were NT control (n = 8), CpG + αPD-1 (n = 6) and ablation + CpG + αPD-1 (Abl + CpG + αPD-1, n = 7). Tumor growth data result from survival study (n = 21) but are representative of trends in 7 studies with varied end points (n = 90 total). (B) Immunotherapy alone and coincident TA-immunotherapy induced suppression of local tumor growth. (C) Contralateral tumor growth suppression was greater for immunotherapy alone. Data plotted as mean ± SEM. (D) By day 180, survival outcomes for mice treated with immunotherapy alone (CpG + αPD-1, n = 6) were improved compared with those treated coincident with ablation (ablation + CpG + αPD-1, n = 7) or control treatments (NT Control [n = 8], αPD-1 [n = 3], CpG [n = 7], ablation [n = 7], and ablation + CpG [n = 4]). (E–H) The fourth and ninth mammary fat pad (tumor and the embedded node) was harvested at day 28, and immunocytes were quantified via flow cytometry (n = 4 per group). Number of (E and F) leukocytes and (G and H) IFN-γ CD8+ T cells in treated (E and G) and contralateral (F and H) tumors. For box-and-whiskers plots, the whiskers represent the minimum and maximum values, the box boundaries represent the 25th and 75th percentiles, and the middle line is the median value. (I) IHC on day 50 verified that both CpG + αPD-1 (n = 3) and ablation + CpG + αPD-1 (n = 3) increased infiltrating CD8+ T cells (brown stain) in contralateral tumors compared with NT controls. C was analyzed using an unpaired t test assuming unequal variance comparing mean tumor volume of CpG + αPD-1 and ablation + CpG + αPD-1 at each day. E–H were analyzed by ANOVA followed by Fisher’s LSD test without multiple comparisons correction. Scale bars: 150 μm.*P < 0.05, **P < 0.01, ***P < 0.001.

Article Snippet: The checkpoint inhibitor, rat anti–mouse PD-1 antibody (αPD-1, RMP1-14) was purchased from Bio X Cell.

Techniques: Injection, Flow Cytometry, Staining

Journal: JCI Insight

Article Title: Priming is key to effective incorporation of image-guided thermal ablation into immunotherapy protocols

doi: 10.1172/jci.insight.90521

Figure Lengend Snippet: CpG+αPD-1 reduces macrophages and myeloid-derived suppressor cells (MDSCs) in contralateral tumors and increases PD-L1 expression in tumor-infiltrating leukocytes. Coincident thermoablative immunotherapy (TA-immunotherapy) increases macrophages in treated tumors. (A–E) Animals were treated as described in Figure 3A with thermal ablation, CpG (100 μg per injection), and αPD-1 (200 μg per injection). Treatment cohorts were NT control (n = 8), CpG + αPD-1 (n = 8), and ablation + CpG + αPD-1 (n = 8). (A and B) The frequency of (A) macrophages and (B) MDSCs in the treated and contralateral tumors following treatment. The fourth and ninth mammary fat pads (tumor and the embedded node) were harvested at day 35 and immunocytes were quantified via flow cytometry. (C–E) Expression of PD-1 and PD-L1 in treated and contralateral tumors. Tumors were harvested at day 28, and immunocytes were quantified via flow cytometry. (C) The amount of PD-1 expressed on CD4+ T cells, the (D) expression of PD-L1 on tumor/stromal cells (CD45–), and (E) the expression of PD-L1 on CD45+ leukocytes in treated and contralateral tumors. For box-and-whiskers plots, the whiskers represent the minimum and maximum values, the box boundaries represent the 25th and 75th percentiles, and the middle line is the median value. Statistics in A–E were determined by ANOVA followed by Fisher’s LSD test without multiple comparisons correction. *P < 0.05, **P < 0.01, ***P < 0.001, ‡P < 0.05 compared with all groups.

Article Snippet: The checkpoint inhibitor, rat anti–mouse PD-1 antibody (αPD-1, RMP1-14) was purchased from Bio X Cell.

Techniques: Derivative Assay, Expressing, Injection, Flow Cytometry

Journal: bioRxiv

Article Title: Pharmacologic activation of the G protein-coupled estrogen receptor inhibits pancreatic ductal adenocarcinoma

doi: 10.1101/365668

Figure Lengend Snippet: ( A ) Experimental timeline of murine PDAC-bearing mice treated with subcutaneously delivered vehicle or 10mg/kg G-1, as well as 10mg/kg αPD-1 antibody or isotype antibody control (2A3), n=5 per group. ( B ) Tumor volumes of 2838c3 PDAC tumors one day after the final treatment with 10mg/kg G-1, n=10 per group, * denotes significance by one-way ANOVA. ( C ) 2838c3 tumor volumes measured over time; line terminates after first survival event in the group, n=5 per group. ( D ) Survival curve of 28383-bearing mice treated with vehicle or 10mg/kg G-1, as well as 10mg/kg αPD-1 antibody or 10mg/kg isotype antibody control (2A3), significance between groups by the Log-Rank (Mantel-Cox) test is listed in the table below. ( E ) Tumor volumes of 6419c5 PDAC tumors one day after the final treatment with 10mg/kg G-1, n=10 per group, * denotes significance by one-way ANOVA. ( F ) 6419c5 tumor volumes measured over time; line terminates after first survival event in the group, n=5 per group. ( G ) Survival curve of 6419c5-bearing mice treated with vehicle or 10mg/kg G-1, as well as 10mg/kg αPD-1 antibody or 10mg/kg isotype antibody control (2A3), significance between groups by the Log-Rank (Mantel-Cox) test is listed in the table below. ( H ) Tumor volumes of 6499c4 PDAC tumors one day after the final treatment with 10mg/kg G-1, n=10 per group, * denotes significance by one-way ANOVA. ( I ) 6499c4 tumor volumes measured over time; line terminates after first survival event in the group, n=5 per group. ( J ) Survival curve of 6499c4-bearing mice treated with vehicle or 10mg/kg G-1, as well as 10mg/kg αPD-1 antibody or 10mg/kg isotype antibody control (2A3), significance between groups by the Log-Rank (Mantel-Cox) test is listed in the table below. ( K ) in situ hybridization for PD-L1 in murine PDAC tumors, 40x magnification, scale bar=50um.

Article Snippet: Isotype control antibody (Clone: 2A3, BioXcell, West Lebanon, NH, USA) and αPD-1 antibody (Clone: RMP1-14, BioXcell) were diluted in sterile PBS and delivered through intraperitoneal injections at a dose of 10mg/kg.

Techniques: In Situ Hybridization