2014
DOI: 10.1158/1535-7163.mct-13-0598
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Pharmacodynamic and Antineoplastic Activity of BI 836845, a Fully Human IGF Ligand-Neutralizing Antibody, and Mechanistic Rationale for Combination with Rapamycin

Abstract: Insulin-like growth factor (IGF) signaling is thought to play a role in the development and progression of multiple cancer types. To date, therapeutic strategies aimed at disrupting IGF signaling have largely focused on antibodies that target the IGF-I receptor (IGF-IR). Here, we describe the pharmacologic profile of BI 836845, a fully human monoclonal antibody that utilizes an alternative approach to IGF signaling inhibition by selectively neutralizing the bioactivity of IGF ligands. Biochemical analyses of B… Show more

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Cited by 86 publications
(85 citation statements)
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“…In contrast, there are only two IGF-1/2 neutralizing mAb in clinical trials currently under investigation [47]. BI836845, mAb targeted against IGF-1/2, showed encouraging results in preclinical models: it reduced the proliferation of human cell lines derived from different cancer types, inhibited tumor growth in a xenograft model and had additive effect in combination with rapamycin [48]; hence, it is now in clinical trial phase II for metastatic breast cancer patients (www.clinicaltrials.gov, NCT02123823). Another anti-IGF1 mAb, MEDI-573 is also in phase II clinical trial currently for late stage breast cancer (www.clinicaltrials.gov, NCT01446159).…”
Section: Discussionmentioning
confidence: 99%
“…In contrast, there are only two IGF-1/2 neutralizing mAb in clinical trials currently under investigation [47]. BI836845, mAb targeted against IGF-1/2, showed encouraging results in preclinical models: it reduced the proliferation of human cell lines derived from different cancer types, inhibited tumor growth in a xenograft model and had additive effect in combination with rapamycin [48]; hence, it is now in clinical trial phase II for metastatic breast cancer patients (www.clinicaltrials.gov, NCT02123823). Another anti-IGF1 mAb, MEDI-573 is also in phase II clinical trial currently for late stage breast cancer (www.clinicaltrials.gov, NCT01446159).…”
Section: Discussionmentioning
confidence: 99%
“…low K d , low IC 50 ) attributes. Increased IGF signaling can potentially limit the efficacy of cytotoxic agents, and IGF-IR inhibition to overcome platinum-resistance in OvCa is by no means a novel concept (41,42). PAPP-A is proposed as a better therapeutic target with greater tumor specificity and lower risk of side effects than other IGF system targets.…”
Section: Discussionmentioning
confidence: 99%
“…Several ATP non-competitive agents are in development, including one at an early stage of clinical testing [27,28]. IGF ligand antibodies act by neutralising IGF-1 and IGF-2, preventing receptor activation without affecting glucose tolerance [22,29]. All three classes of agent have anti-tumour activity in vitro and in vivo , although it should be acknowledged that some preclinical models were selected or designed to be IGF responsive, and relatively limited preclinical data led to an extremely large number of clinical trials [30].…”
Section: Igf-targeting: a Promising Startmentioning
confidence: 99%