invivoplus anti mouse pd 1 cd279  (Bio X Cell)

Journal: iScience

Article Title: Identification of a group of 9-amino-acridines that selectively downregulate regulatory T cell functions through FoxP3

doi: 10.1016/j.isci.2025.111931

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Article Snippet: InVivoPlus rat IgG2a isotype control and InVivoPlus anti-mouse PD-1 (CD279) were purchased from BioXcell.

Techniques: Control, Binding Assay, Staining, Virus, Recombinant, Avidin-Biotin Assay, Cell Isolation, Activation Assay, Amplified Luminescent Proximity Homogenous Assay, Software

Journal: Cancer Discovery

Article Title: Botensilimab, an Fc-Enhanced Anti–CTLA-4 Antibody, Is Effective against Tumors Poorly Responsive to Conventional Immunotherapy

doi: 10.1158/2159-8290.CD-24-0190

Figure Lengend Snippet: Botensilimab enhances T-cell responsiveness independent of FcγRIIIA allele status and reduces Treg frequency. A, Binding of botensilimab, IgG1 variant of botensilimab (parental IgG1), or aglycosylated IgG1 N297A isotype negative control antibody to CHO cells expressing FcγRIIIA V158 or F158 by flow cytometry. MFI, mean fluorescence intensity. B, Signaling through FcγRIIIA V158 and FcγRIIIA F158 in Jurkat cells expressing FcγRs upstream of an NFAT-dependent luciferase reporter, cocultured with CTLA-4–expressing cells and botensilimab, parental IgG1, IgG1 DLE isotype, or IgG1 isotype. Luciferase expression shown as relative light units (RLU). C, Schematic depicting botensilimab binding to CTLA-4–expressing T cells and coengaging FcγRIIIA-expressing APC or (NK cells to create an immune synapse). D, IL2 secretion from SEA-stimulated healthy donor PBMC from FcγRIIIA homozygote V/V 158, FcγRIIIA heterozygote V/F 158, and FcγRIIIA homozygote F/F 158 donors treated with botensilimab, parental IgG1, or IgG1 DLE isotype. E, IL10, soluble CD25 (sCD25), and TGFβ1 secretion from SEA-stimulated PBMC treated with 5 μg/mL botensilimab, parental IgG1, or IgG1 DLE . FcγRIIIA heterozygote V/F 158 donor shown. F, Treg (CD3 + CD4 + CD25 + FOXP3 + ) frequencies from SEA-stimulated healthy donor PBMCs treated with 5 μg/mL of botensilimab, parental IgG1, or IgG1 DLE by flow cytometry ( n = 4 donors). G, Dye-labeled and caspase 3/7–stained primary CD4 + FOXP3 + Tregs or ( H ) conventional CD4 + T cells cocultured at a 1:1 ratio with FcγRIIIA-expressing NK-92 cells treated with indicated antibodies. Values measured by live imaging using confocal microscopy ( n = 3). Data are represented as mean ± SEM ( A , B , and D–G ). Data analyzed by two-way ANOVA ( A , B , D , and F–H ) or one-way ANOVA ( E ), all followed by the Tukey multiple comparisons test.

Article Snippet: InVivoPlus grade isotype control (clone MPC-11, mIgG2b) and mouse reactive anti–PD-1 (RMP1-14; Rat IgG2a, κ) were obtained from Bio X Cell.

Techniques: Binding Assay, Variant Assay, Negative Control, Expressing, Flow Cytometry, Fluorescence, Luciferase, Labeling, Staining, Imaging, Confocal Microscopy

Journal: Cancer Discovery

Article Title: Botensilimab, an Fc-Enhanced Anti–CTLA-4 Antibody, Is Effective against Tumors Poorly Responsive to Conventional Immunotherapy

doi: 10.1158/2159-8290.CD-24-0190

Figure Lengend Snippet: Botensilimab enhances the frequency of activated myeloid, NK, B, and NKT cells. A, Global t -distributed stochastic neighbor embedding (t-SNE) maps of total live immune cells (CD45 + ) after stimulation with SEA in the presence of 5 μg/mL botensilimab, parental IgG1, or IgG1 DLE isotype. PBMC from five FcγRIIIA V/F 158 heterozygote healthy donors were used. Six phenotypically distinct clusters identified by individual phenotypic markers by flow cytometry within concatenated total live immune cells analyzed. Log 2 fold changes in ( B ) CD16 − NK, ( C ) B, ( D ) NKT, ( E ) DC, ( F ) monocyte, and ( G ) CD16 + NK cell counts in each immune cell cluster between samples treated with botensilimab and parental IgG1, compared with IgG1 DLE isotype ( n = 5/group; data are paired). H, Activated CD16 + CD11c + ( I ) and CD16 − CD11c + myeloid cell frequency determined by CD40, HLA-DR, and CD86 expression by flow cytometry. Representative data from an FcγRIIIA V/F 158 heterozygote donor. Data are represented as mean ± SEM ( H and I ). Data analyzed with a two-tailed paired t test ( B–G ) or one-way ANOVA followed by a Tukey multiple comparisons test ( H and I ).

Article Snippet: InVivoPlus grade isotype control (clone MPC-11, mIgG2b) and mouse reactive anti–PD-1 (RMP1-14; Rat IgG2a, κ) were obtained from Bio X Cell.

Techniques: Flow Cytometry, Expressing, Two Tailed Test

Journal: Cancer Discovery

Article Title: Botensilimab, an Fc-Enhanced Anti–CTLA-4 Antibody, Is Effective against Tumors Poorly Responsive to Conventional Immunotherapy

doi: 10.1158/2159-8290.CD-24-0190

Figure Lengend Snippet: Clinical response to botensilimab monotherapy and combination with balstilimab in patients with advanced solid cancers. Waterfall plot of maximal percentage change from baseline in sum of tumor target lesion diameters for patients treated with botensilimab monotherapy or in combination with balstilimab ( A ) who progressed on prior ICI [αPD-(L)1 and/or αCTLA-4] therapy ( n = 53), ( B ) received prior αCTLA-4 therapy [ipilimumab, QL1706 (a mixture of αPD-1 IgG4 and αCTLA-4 IgG1; δ) or ALPN-202 (a dual PD-L1/CTLA-4 blocker and CD28 costimulator; ϕ; n = 7], or ( C ) received no prior ICI therapy ( n = 135). Only patients treated with 1, 2, 3 mg/kg, or 150 mg of botensilimab monotherapy (red bar) or in combination with 3 mg/kg or 450 mg balstilimab (blue bar) are shown. Tumor reduction was assessed according to RECIST 1.1 criteria. Lower dotted line demarcates tumor reduction of 30%. * Indicates confirmed responses as of March 27, 2023.

Article Snippet: InVivoPlus grade isotype control (clone MPC-11, mIgG2b) and mouse reactive anti–PD-1 (RMP1-14; Rat IgG2a, κ) were obtained from Bio X Cell.

Techniques:

Journal: Cancer Discovery

Article Title: Botensilimab, an Fc-Enhanced Anti–CTLA-4 Antibody, Is Effective against Tumors Poorly Responsive to Conventional Immunotherapy

doi: 10.1158/2159-8290.CD-24-0190

Figure Lengend Snippet: Botensilimab enhances activated T-cell prevalence, reduces intratumoral Tregs, and upregulates genes associated with T cell–inflamed tumors in patients with advanced solid cancers. A–G, Pretreatment (pre-tx) and on-treatment (on-tx) blood samples from patients treated with 1 or 2 mg/kg botensilimab monotherapy. PBMC analyzed by flow cytometry for the ( A ) frequency of ICOS + and ( B ) HLA-DR mean fluorescence intensity (MFI) on CD4 + Teff (CXCR3 + ) and ( C ) frequency of Ki-67 + CD4 and CD8 effector memory (Tem, CD45RO + CCR7 − ) T-cell subsets ( n = 28; on-tx: 7 days after first dose). D, Plasma IFNγ in pre- and on-tx samples ( n = 23; on-tx: 24 hours after first dose). Number of ( E ) expanded vs. contracted and ( F ) newly expanded vs. lost T-cell clonotypes in pre-tx vs. on-tx blood by differential abundance analysis between baseline (pre-tx; cycle 1 day 1) and 3–4 weeks postdose ( n = 15; pre-tx: cycle 1 day 1; on-tx: 3–4 weeks after first dose). P values compare expanded vs. contracted T-cell clonotypes in E and F . G, T-cell clonotype abundance in two representative patients treated with 0.1 or 2 mg/kg botensilimab every 3 weeks. CDR3 sequencing of human TCRβ chains performed using immunoSEQ. H, Intratumoral cell type enrichment scores calculated using xCell for Tregs, CD4 + non-Tregs, CD8 + T cells, and macrophages as determined from RNA-seq of pre-tx and on-tx tumor biopsies from patients treated with 1 or 2 mg/kg botensilimab monotherapy every 3 or 6 weeks ± balstilimab every 2 weeks ( n = 26; on-tx: cycle 2 day 1 for every 6-week cohort, or cycle 3 day 1 for every 3-week cohort). I, Percent peripheral Treg (CD4 + , CD127 low/− , CD25 + ) subsets ( n = 28; on-tx: 7 days after first dose) analyzed by flow cytometry from patients treated with 1 or 2 mg/kg botensilimab monotherapy. J, Intratumoral CXCL9 and CXCL10 and CCL5 gene expression and ( K ) IFNγ and T cell–inflamed gene expression signatures as determined from RNA-seq of pre-tx and on-tx tumor biopsies ( n = 26). L, IL2 secretion from SEA-stimulated PBMC from FcγRIIIA heterozygote V/F 158 and FcγRIIIA homozygote F/F 158 donors treated with botensilimab, parental IgG1, or IgG1 DLE isotype, alone ± αPD-1 (balstilimab). Paired data points with group mean ( A–D and H–K ) or mean ± SEM ( L ). Data analyzed with the two-tailed Wilcoxon matched-paired t test ( A–F and H–K ) or two-way ANOVA with the Tukey multiple comparisons test ( L ).

Article Snippet: InVivoPlus grade isotype control (clone MPC-11, mIgG2b) and mouse reactive anti–PD-1 (RMP1-14; Rat IgG2a, κ) were obtained from Bio X Cell.

Techniques: Flow Cytometry, Fluorescence, Sequencing, RNA Sequencing Assay, Expressing, Two Tailed Test