10530Background: Long-term infusion (LTI) of the anti-GD2 antibody (Ab) ch14.18/CHO in combinatio... more 10530Background: Long-term infusion (LTI) of the anti-GD2 antibody (Ab) ch14.18/CHO in combination with interleukin-2 (IL-2) prolongs survival in patients (pts) with high-risk neuroblastoma compare...
10563Background: Long-term infusion (LTI) emerges as a promising new delivery method of ch14.18/C... more 10563Background: Long-term infusion (LTI) emerges as a promising new delivery method of ch14.18/CHO for relapsed/refractory neuroblastoma patients. The role of concomitant treatment with scIL2 is u...
e21171 Background: The RAS is known for regulation of blood pressure. However, an activated RAS a... more e21171 Background: The RAS is known for regulation of blood pressure. However, an activated RAS also supports tumor growth, in particular by its effector peptide Ang II. Elevated Ang II levels were found in plasma and malignant effusions of cancer patients (Samonigg et al. ASCO 2010). We have developed a sensitive LC-MS method to quantify plasma levels of all relevant peptides of the RAS. Utilization of this method for analysis of plasma of cancer patients, resulting in a "RAS peptide fingerprint" gives insight into the activation pattern of the RAS and may be utilized as guidance for novel therapies that re-balance an activated RAS, thereby reverting a tumor growth-promoting environment. METHODS A sensitive method based on LC-MS was developed to quantify Ang peptides and metabolites in plasma in a single run. Plasma was obtained from various patients with solid cancers in advanced stage and levels of Ang I, Ang II, Ang III, Ang IV, Ang1-9, Ang1-7, Ang2-7, Ang3-7 and Ang1-5 assessed. Respective results found in 21 healthy volunteers served as comparison. RESULTS In all analysed cancer patients (n=13) an activated RAS was seen. Substantially elevated Ang peptide plasma levels were found (in pg/ml): Ang I: mean 1.900, range 90-12.000 (mean healthy 17); Ang II: mean 350, range 5-2.100 (mean healthy 8); Ang1-9: mean 22, range 3-160 (mean healthy 3) Ang1-7: mean 45, range 5-250 (mean healthy 3); Ang1-5: mean 23, range 2-120 (mean healthy 2). CONCLUSIONS Ang peptide levels in cancer patients were massively elevated when compared to healthy controls (up to 100-fold). Highly elevated levels were found for the effector peptide Ang II and its precursor Ang I, indicating overactivity of Renin and ACE. Degradation products of Ang II such as Ang1-7 and Ang1-5 were also elevated. Interestingly, the activation of the RAS did not have obvious impact on blood pressure. Based on these results, a novel therapeutic modality against cancer may consist in re-balancing an activated RAS. In this regard, treatment of cancer patients with recombinant human ACE2 (which efficiently degrades Ang II to Ang1-7 and is in clinical development against diseases with an imbalanced RAS) may be considered.
10530Background: Long-term infusion (LTI) of the anti-GD2 antibody (Ab) ch14.18/CHO in combinatio... more 10530Background: Long-term infusion (LTI) of the anti-GD2 antibody (Ab) ch14.18/CHO in combination with interleukin-2 (IL-2) prolongs survival in patients (pts) with high-risk neuroblastoma compare...
10563Background: Long-term infusion (LTI) emerges as a promising new delivery method of ch14.18/C... more 10563Background: Long-term infusion (LTI) emerges as a promising new delivery method of ch14.18/CHO for relapsed/refractory neuroblastoma patients. The role of concomitant treatment with scIL2 is u...
e21171 Background: The RAS is known for regulation of blood pressure. However, an activated RAS a... more e21171 Background: The RAS is known for regulation of blood pressure. However, an activated RAS also supports tumor growth, in particular by its effector peptide Ang II. Elevated Ang II levels were found in plasma and malignant effusions of cancer patients (Samonigg et al. ASCO 2010). We have developed a sensitive LC-MS method to quantify plasma levels of all relevant peptides of the RAS. Utilization of this method for analysis of plasma of cancer patients, resulting in a "RAS peptide fingerprint" gives insight into the activation pattern of the RAS and may be utilized as guidance for novel therapies that re-balance an activated RAS, thereby reverting a tumor growth-promoting environment. METHODS A sensitive method based on LC-MS was developed to quantify Ang peptides and metabolites in plasma in a single run. Plasma was obtained from various patients with solid cancers in advanced stage and levels of Ang I, Ang II, Ang III, Ang IV, Ang1-9, Ang1-7, Ang2-7, Ang3-7 and Ang1-5 assessed. Respective results found in 21 healthy volunteers served as comparison. RESULTS In all analysed cancer patients (n=13) an activated RAS was seen. Substantially elevated Ang peptide plasma levels were found (in pg/ml): Ang I: mean 1.900, range 90-12.000 (mean healthy 17); Ang II: mean 350, range 5-2.100 (mean healthy 8); Ang1-9: mean 22, range 3-160 (mean healthy 3) Ang1-7: mean 45, range 5-250 (mean healthy 3); Ang1-5: mean 23, range 2-120 (mean healthy 2). CONCLUSIONS Ang peptide levels in cancer patients were massively elevated when compared to healthy controls (up to 100-fold). Highly elevated levels were found for the effector peptide Ang II and its precursor Ang I, indicating overactivity of Renin and ACE. Degradation products of Ang II such as Ang1-7 and Ang1-5 were also elevated. Interestingly, the activation of the RAS did not have obvious impact on blood pressure. Based on these results, a novel therapeutic modality against cancer may consist in re-balancing an activated RAS. In this regard, treatment of cancer patients with recombinant human ACE2 (which efficiently degrades Ang II to Ang1-7 and is in clinical development against diseases with an imbalanced RAS) may be considered.
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Papers by Hans Loibner