Journal: Journal of Cachexia, Sarcopenia and Muscle

Article Title: Targeting Cancer Cachexia: A Mechanistic Evaluation of Anti‐GDF‐15 Antibody‐Based Combination Therapies

doi: 10.1002/jcsm.70312

Figure Lengend Snippet: Anti‐myostatin antibody treatment has limited efficacy to improve cachexia, when given alone, in a tumour model (HT‐1080) with high circulating GDF‐15 elevation. (a, b) Circulating plasma levels of (a) GDF‐15 and (b) myostatin in NTB and HT‐1080 tumour‐bearing mice at the end of study ( n = 8–10 per group). (c) Tumour‐free body weight percentage change in NTB and HT‐1080 tumour‐bearing mice treated with either control IgG, anti‐GDF‐15 antibody or anti‐myostatin antibody during the study ( n = 9–10 per group). (d) Daily food intake at the end of study ( n = 8–10 per group). (e, f) Body composition, including (e) fat and lean mass and (f) gastrocnemius weight at the end of study ( n = 9–10 per group). Data are mean ± SEM. * p < 0.05, ** p < 0.01, **** p < 0.0001 vs. NTB; ## p < 0.01, #### p < 0.0001 vs. HT‐1080; ^ p < 0.05 vs. HT‐1080 + anti‐myostatin. GDF‐15, growth differentiation factor‐15; IgG, immunoglobulin G; LLOD, lower limit of detection; NTB, non–tumour‐bearing; SEM, standard error of the mean.

Article Snippet: IgG control, anti‐GDF‐15 antibodies (10 mg/kg) and anti‐myostatin antibody (30 mg/kg) were generated by Pfizer and administered via subcutaneous injection once every 3 days (except in the RENCA and TOV21G tumour models, where it was administered once per week).

Techniques: Clinical Proteomics, Control

Journal: Journal of Cachexia, Sarcopenia and Muscle

Article Title: Targeting Cancer Cachexia: A Mechanistic Evaluation of Anti‐GDF‐15 Antibody‐Based Combination Therapies

doi: 10.1002/jcsm.70312

Figure Lengend Snippet: Anti‐myostatin antibody treatment has limited efficacy to improve cachexia, when given alone or in combination with anti‐GDF‐15 antibody, in a tumour model (HT‐1080) with high circulating GDF‐15 elevation. (a) Tumour‐free body weight percentage change in NTB and HT‐1080 tumour‐bearing mice treated with either control IgG, anti‐GDF‐15 antibody or the combination of anti‐GDF‐15 antibody and anti‐myostatin antibody during the study. (b) Cumulative food intake during the treatment period (Days 9–14). (c–e): Body composition, including (c) fat mass, (d) lean mass and (e) hindlimb muscle mass at the end of study. (f) Maximum force at 125 and 150 Hz in the muscle function test. N = 12–16 per group for a–f. Data are mean ± SEM. * p < 0.05, **** p < 0.0001 vs. NTB; # p < 0.05; ## p < 0.01, ### p < 0.001; #### p < 0.0001 vs. HT‐1080. GDF‐15, growth differentiation factor‐15; IgG, immunoglobulin G; NTB, non–tumour‐bearing; SEM, standard error of the mean.

Article Snippet: IgG control, anti‐GDF‐15 antibodies (10 mg/kg) and anti‐myostatin antibody (30 mg/kg) were generated by Pfizer and administered via subcutaneous injection once every 3 days (except in the RENCA and TOV21G tumour models, where it was administered once per week).

Techniques: Control

Journal: Journal of Cachexia, Sarcopenia and Muscle

Article Title: Targeting Cancer Cachexia: A Mechanistic Evaluation of Anti‐GDF‐15 Antibody‐Based Combination Therapies

doi: 10.1002/jcsm.70312

Figure Lengend Snippet: Anti‐myostatin antibody treatment has limited efficacy to improve cachexia when given alone or in combination with anti‐GDF‐15 antibody in a mouse tumour model (RENCA) with high circulating GDF‐15 elevation. (a, b) Circulating plasma levels of (a) GDF‐15 and (b) myostatin in NTB and RENCA tumour‐bearing mice at the end of study ( n = 5–10 for NTB; n = 11 for RENCA). (c) Tumour‐free body weight percentage change in NTB and RENCA tumour‐bearing mice treated with control IgG, anti‐myostatin antibody or anti‐GDF‐15 antibody alone or in combination with anti‐myostatin antibody during the study. (d, e) Body composition, including (d) lean and fat mass and (e) hindlimb muscle mass at the end of study. (f) Maximum force at 150 Hz in the muscle function test. n = 8–16 per group for c–f. Data are mean ± SEM. ** p < 0.01, *** p < 0.001, **** p < 0.0001 vs. NTB; # p < 0.05; ## p < 0.01, ### p < 0.001; #### p < 0.0001 vs. RENCA; ^ p < 0.05, ^^ p < 0.01, ^^^p < 0.001, ^^^^ p < 0.0001, for all other comparisons between RENCA groups treated with anti‐myostatin and/or anti‐GDF‐15. GDF‐15, growth differentiation factor‐15; IgG, immunoglobulin G; NTB, non–tumour‐bearing; SEM, standard error of the mean.

Article Snippet: IgG control, anti‐GDF‐15 antibodies (10 mg/kg) and anti‐myostatin antibody (30 mg/kg) were generated by Pfizer and administered via subcutaneous injection once every 3 days (except in the RENCA and TOV21G tumour models, where it was administered once per week).

Techniques: Clinical Proteomics, Control

Journal: Journal of Cachexia, Sarcopenia and Muscle

Article Title: Targeting Cancer Cachexia: A Mechanistic Evaluation of Anti‐GDF‐15 Antibody‐Based Combination Therapies

doi: 10.1002/jcsm.70312

Figure Lengend Snippet: Anti‐myostatin antibody treatment improves cachexia when given alone or in combination with anti‐GDF‐15 antibody in a tumour model (TOV21G) with low circulating GDF‐15 elevation. (a, b) Circulating plasma levels of (a) GDF‐15 and (b) myostatin in NTB and TOV21G tumour‐bearing mice at the end of study ( n = 8 per group). (c) Tumour‐free body weight percentage change in NTB and TOV21G tumour‐bearing mice treated with control IgG or anti‐GDF‐15 antibody alone or in combination with anti‐myostatin antibody during the study. (d–f) Body composition, including (d) fat mass, (e) lean mass and (f) hindlimb muscle mass at the end of study. n = 15–17 per group for c–f. Data are mean ± SEM. ** p < 0.01, **** p < 0.0001 vs. NTB; # p < 0.05, ## p < 0.01, #### p < 0.0001 vs. TOV21G; ^^^ p < 0.001, ^^^^ p < 0.0001, for comparison between TOV21G + anti‐GDF‐15 and TOV21G + anti‐GDF‐15 + anti‐myostatin. GDF‐15, growth differentiation factor‐15; IgG, immunoglobulin G; LLOD, lower limit of detection; NTB, non–tumour‐bearing; SEM, standard error of the mean.

Article Snippet: IgG control, anti‐GDF‐15 antibodies (10 mg/kg) and anti‐myostatin antibody (30 mg/kg) were generated by Pfizer and administered via subcutaneous injection once every 3 days (except in the RENCA and TOV21G tumour models, where it was administered once per week).

Techniques: Clinical Proteomics, Control, Comparison

Journal: Journal of Cachexia, Sarcopenia and Muscle

Article Title: Targeting Cancer Cachexia: A Mechanistic Evaluation of Anti‐GDF‐15 Antibody‐Based Combination Therapies

doi: 10.1002/jcsm.70312

Figure Lengend Snippet: Anti‐myostatin antibody treatment improves muscle function when given alone or in combination with anti‐GDF‐15 antibody in a tumour model (TOV21G) with low circulating GDF‐15 elevation. (a) Maximum force at 125 and 150 Hz in the muscle function test. (b, c) A treadmill endurance test was conducted at the end of the study with (b) running distance measured and (c) work calculated accounting for the effect of body weight on treadmill performance. N = 15–17 per group for a–c. Data are mean ± SEM. **** p < 0.0001 vs. NTB; # p < 0.05, ## p < 0.01, #### p < 0.0001 vs. TOV21G. GDF‐15, growth differentiation factor‐15; NTB, non–tumour‐bearing; SEM, standard error of the mean.

Article Snippet: IgG control, anti‐GDF‐15 antibodies (10 mg/kg) and anti‐myostatin antibody (30 mg/kg) were generated by Pfizer and administered via subcutaneous injection once every 3 days (except in the RENCA and TOV21G tumour models, where it was administered once per week).

Techniques:

Journal: Journal of Cachexia, Sarcopenia and Muscle

Article Title: Targeting Cancer Cachexia: A Mechanistic Evaluation of Anti‐GDF‐15 Antibody‐Based Combination Therapies

doi: 10.1002/jcsm.70312

Figure Lengend Snippet: The effect of anti‐myostatin antibody is decreased by the presence of GDF‐15 in healthy mice. (a) Body weight percentage change in healthy mice treated with control IgG (Veh) or anti‐myostatin antibody during the study. (b, c) Body composition, including (b) fat and lean mass and (c) hindlimb muscle mass at the end of study in healthy mice. (d) Body weight percentage change in healthy mice treated with Fc‐GDF‐15 alone (with control IgG) or in the presence of anti‐GDF‐15 antibody or anti‐myostatin antibody. Veh control received PBS and IgG. (e, f) Body composition, including (e) fat and lean mass and (f) hindlimb muscle mass at the end of study in healthy mice treated with vehicle or Fc‐GDF‐15 alone or in the presence of anti‐GDF‐15 or anti‐myostatin antibody. N = 15 per group for a–f. Data are mean ± SEM. **** p < 0.0001 vs. Veh; # p < 0.05, #### p < 0.0001 vs. Fc‐GDF‐15; ^ p < 0.05, Fc‐GDF‐15 + anti‐myostatin vs. Fc‐GDF‐15 + anti‐GDF‐15. GDF‐15, growth differentiation factor‐15; IgG, immunoglobulin G; PBS, phosphate‐buffered saline; SEM, standard error of the mean; Veh, vehicle.

Article Snippet: IgG control, anti‐GDF‐15 antibodies (10 mg/kg) and anti‐myostatin antibody (30 mg/kg) were generated by Pfizer and administered via subcutaneous injection once every 3 days (except in the RENCA and TOV21G tumour models, where it was administered once per week).

Techniques: Control, Saline