medi9447  (MedImmune llc)

Journal: Nature Communications

Article Title: An antibody cocktail targeting two different CD73 epitopes enhances enzyme inhibition and tumor control

doi: 10.1038/s41467-024-55207-9

Figure Lengend Snippet: A Flow cytometry analysis of HB0038 and HB0039 binding to CHO-S cells stably overexpressing human CD73 protein. For clarity, “38” refers to HB0038 and “39” refers to HB0039 in subsequent references. Results represent two technical replicates from one of three independent experiments; data are presented as mean values ± SD. B Soluble CD73 activity inhibition by HB0038, HB0039, HB0045, Oleclumab, Mupadolimab, and AK119. Inhibition efficiency was calculated using Eq. as described in the Methods section. Results represent three technical replicates from one of three independent experiments; data are presented as mean values ± SD. C Membrane-bound CD73 activity inhibition by HB0038, HB0039, HB0045, Oleclumab, and lgG control. Inhibition efficiency was calculated using Eq. as described in the Methods section. mCD73: membrane-bound CD73. Results represent two technical replicates from one of three independent experiments; data are presented as mean values ± SD. D CD73 activity inhibition by HB0038, HB0039, and HB0045, CD73 MIX indicates a mixture of soluble and membrane-bound CD73. Inhibition efficiency was calculated using Eq. as described in the Methods section. Results represent two technical replicates from one of three independent experiments; data are presented as mean values ± SD. E , F Antibody-mediated proliferation in CD4 + and CD8 + T cells with dose-dependent HB0038, HB0039, or HB0045. Stim: anti-CD3 antibody + anti-CD28 antibody + IL-7. Workflow refers to Supplementary Fig. . Results represent two technical replicates from one of three independent experiments; data are presented as mean values ± SD.

Article Snippet: The latter strategy is utilized by several therapeutic antibodies, including Oleclumab (MEDI9447), which is currently in clinical Phase 3 development by AstraZeneca .

Techniques: Flow Cytometry, Binding Assay, Stable Transfection, Activity Assay, Inhibition, Membrane, Control

Journal: Nature Communications

Article Title: An antibody cocktail targeting two different CD73 epitopes enhances enzyme inhibition and tumor control

doi: 10.1038/s41467-024-55207-9

Figure Lengend Snippet: A Workflow illustrating CD73 antibody treatment across different tumors in PBMC-humanized NPG-immunodeficient mice. “I.P.” denotes intraperitoneal injections; “BIW” indicates administration twice weekly. It was created in BioRender. Zhifeng, Y. (2024) https://BioRender.com/r91t302 . B Impact of varying anti-CD73 antibody doses on MDA-MB-231 tumor growth and weight in PBMC-humanized NPG mice. Once tumors reached an average size of 50 ~ 100 mm³, mice bearing tumors were grouped randomly into six segments ( n = 8) and administered i.v with 1 × 10 7 PBMCs. Treatments were inclusive of the IgG negative control (3 mg/kg), in-house Oleclumab (1 mg/kg), HB0038 (1 mg/kg), HB0039 (1 mg/kg), and HB0045 at two dosages (1 mg/kg and 3 mg/kg). Treatment commenced on the same day with bi-weekly intraperitoneal antibody dosing for 4 weeks. P_volume (38 1 mg/kg vs 45 1 mg/kg) = 0.0087; P_volume (Oleclumab 1 mg/kg vs 45 1 mg/kg) <0.0001; P_volume (Oleclumab 1 mg/kg vs 45 3 mg/kg) <0.0001; P_weight (Oleclumab 1 mg/kg vs control 3 mg/kg) <0.0001; P_weight (Oleclumab 1 mg/kg vs 45 1 mg/kg) = 0.0141; P_weight (45 1 mg/kg vs 45 3 mg/kg) = 0.004. C NPG mice received a subcutaneous inoculation of BxPC-3 (5 × 10 6 ) in Matrigel on their right flank. Upon tumors achieving an average size of 68 mm³, mice with tumors were grouped randomly into four segments ( n = 6) and administered i.v with 1 × 10 7 PBMCs. Treatments began on day one, with bi-weekly intraperitoneal antibody dosing spanning four weeks. P < 0.0001. D The HB0045 antibody cocktail (anti-CD73), coupled with the HB0025 antibody (anti-PD-L1/VEGF bispecific antibody) and HB0027 (anti-4-1BB antibody), demonstrated potent antitumor capabilities in the A375 melanoma models using PBMC-humanized NPG mice ( n = 6). Unless otherwise specified, the concentration of antibody used in samples was 1 mg/kg. P_volume (Vehicle vs 45) < 0.0001; P_volume (45 vs 25 + 45) = 0.0013; P_volume (25 + 45 vs 25 + 45 + 27) = 0.008; P_weight (Vehicle vs 45) < 0.0001; P_weight (27 vs 25 + 45 + 27) = 0.0054. Prism was employed to compute P values for tumor volumes using two-way ANOVA coupled with Tukey’s multiple-comparison test. For tumor weights, P values were determined using a one-way ANOVA. * P < 0.05, ** P < 0.01, **** P < 0.0001. Data are presented as mean values ± SEM.

Article Snippet: The latter strategy is utilized by several therapeutic antibodies, including Oleclumab (MEDI9447), which is currently in clinical Phase 3 development by AstraZeneca .

Techniques: Negative Control, Control, Concentration Assay, Comparison

Journal: Frontiers in Immunology

Article Title: Manipulating regulatory T cells: is it the key to unlocking effective immunotherapy for pancreatic ductal adenocarcinoma?

doi: 10.3389/fimmu.2024.1406250

Figure Lengend Snippet: T reg -targeted immunotherapies in current development (as of 01/05/2024).

Article Snippet: Oleclumab (MEDI9447) , AstraZeneca , Anti-CD73 monoclonal antibody , Phase II, in combination with chemotherapy and durvalumab (anti-PD-L1), in patients with resectable/borderline resectable PDAC , NCT04940286.

Techniques: Recombinant