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Target Overview
Leukemia inhibitory factor (LIF) is an IL-6 family member involved in embryonic stem cell maintenance and protection from maternal immune attack. Emerging evidence indicates that LIF biology is hijacked by some tumors to promote immunosuppressive tumor-associated macrophages, cancer-initiating cells, and epithelial-mesenchymal transition (EMT).1,2 High levels of LIF are associated with poor clinical outcomes in cancer patients treated with immune checkpoint blockade therapy.3 Pharmacological blockade of LIF represents an exciting first-in-class opportunity to sensitize tumors to IO and chemotherapy by targeting its unique multifaceted biology.4
Compound Overview
AZD0171 is an investigational, humanized monoclonal antibody (mAb), immunoglobulin G subclass 1 (IgG1), which potently and specifically binds to LIF, thereby preventing its interaction with gp130 and LIF receptor activation.
Mechanism of Action
References
1. Shi Y, Gao W, Lytle NK, et al. Nature. 2019;569(7754):131-135. 2. Wang MT, Fer N, Galeas J, et al. Nat Commun. 2019;10(1):3055. 3. Loriot Y, Marabelle A, Guégan JP, et al. Ann Oncol. 2021;32(11):1381-1390. 4. Pascual-García M, Bonfill-Teixidor E, Planas-Rigol E, et al. Nat Commun. 2019;10(1):2416.
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Abbreviations
EMT
epithelial-mesenchymal transition
gp130
glycoprotein 130
IgG1
immunoglobulin G1
LIF
leukemia inhibitory factor
mAb
monoclonal antibody
NSCLC
non-small cell lung cancer
PDC
platinum doublet chemotherapy
Target Overview
Leukemia inhibitory factor (LIF) is an IL-6 family member involved in embryonic stem cell maintenance and protection from maternal immune attack. Emerging evidence indicates that LIF biology is hijacked by some tumors to promote immunosuppressive tumor-associated macrophages, cancer-initiating cells, and epithelial-mesenchymal transition (EMT).1,2 High levels of LIF are associated with poor clinical outcomes in cancer patients treated with immune checkpoint blockade therapy.3 Pharmacological blockade of LIF represents an exciting first-in-class opportunity to sensitize tumors to IO and chemotherapy by targeting its unique multifaceted biology.4
Compound Overview
AZD0171 is an investigational, humanized monoclonal antibody (mAb), immunoglobulin G subclass 1 (IgG1), which potently and specifically binds to LIF, thereby preventing its interaction with gp130 and LIF receptor activation.
Mechanism of Action
References
1. Shi Y, Gao W, Lytle NK, et al. Nature. 2019;569(7754):131-135. 2. Wang MT, Fer N, Galeas J, et al. Nat Commun. 2019;10(1):3055. 3. Loriot Y, Marabelle A, Guégan JP, et al. Ann Oncol. 2021;32(11):1381-1390. 4. Pascual-García M, Bonfill-Teixidor E, Planas-Rigol E, et al. Nat Commun. 2019;10(1):2416.
Clinical trial information
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Abbreviations
EMT
epithelial-mesenchymal transition
gp130
glycoprotein 130
IgG1
immunoglobulin G1
LIF
leukemia inhibitory factor
mAb
monoclonal antibody
NSCLC
non-small cell lung cancer
PDC
platinum doublet chemotherapy