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Surface plasmon resonance analysis of IL-2 and SHR-1916 binding to IL-2Rα and <t>IL-2Rβ.</t> ( A ) IL-2 binds to IL-2Rα. ( B ) SHR-1916 binds to IL-2Rα. ( C ) IL-2 binds to IL-2Rβ. ( D ) SHR-1916 binds to IL-2Rβ.
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Surface plasmon resonance analysis of IL-2 and SHR-1916 binding to IL-2Rα and IL-2Rβ. ( A ) IL-2 binds to IL-2Rα. ( B ) SHR-1916 binds to IL-2Rα. ( C ) IL-2 binds to IL-2Rβ. ( D ) SHR-1916 binds to IL-2Rβ.

Journal: Drug Design, Development and Therapy

Article Title: SHR-1916: A Novel PEGylated Interleukin-2 Analogue with Altered Cellular Selectivity and Improved Pharmacokinetic Profiles for Cancer Immunotherapy

doi: 10.2147/DDDT.S493011

Figure Lengend Snippet: Surface plasmon resonance analysis of IL-2 and SHR-1916 binding to IL-2Rα and IL-2Rβ. ( A ) IL-2 binds to IL-2Rα. ( B ) SHR-1916 binds to IL-2Rα. ( C ) IL-2 binds to IL-2Rβ. ( D ) SHR-1916 binds to IL-2Rβ.

Article Snippet: The human CD25/IL-2Rα with a His-tag (Sino Biological, 10165-H08H) or CD122/IL-2Rβ with a His-tag (Sino Biological, 10696-H08B) was then immobilized.

Techniques: SPR Assay, Binding Assay

Affinity Analysis of IL-2 and SHR-1916 to IL-2Rα and IL-2Rβ

Journal: Drug Design, Development and Therapy

Article Title: SHR-1916: A Novel PEGylated Interleukin-2 Analogue with Altered Cellular Selectivity and Improved Pharmacokinetic Profiles for Cancer Immunotherapy

doi: 10.2147/DDDT.S493011

Figure Lengend Snippet: Affinity Analysis of IL-2 and SHR-1916 to IL-2Rα and IL-2Rβ

Article Snippet: The human CD25/IL-2Rα with a His-tag (Sino Biological, 10165-H08H) or CD122/IL-2Rβ with a His-tag (Sino Biological, 10696-H08B) was then immobilized.

Techniques: Binding Assay

Comprehensive study design and key findings of this research. ( a ) Binding affinity measurements by SPR show that SHR-1916 exhibits a significant IL-2Rβ-binding bias compared to IL-2 and reduced binding affinity to IL-2Rα. ( b ) and ( c ) In vitro cell proliferation assays using CTLL-2 and M07e cells demonstrate that SHR-1916 shows significantly lower proliferation efficiency in cell lines that express the high-affinity IL-2Rαβγ, while its impact on proliferation efficiency is less pronounced in cell lines that express the intermediate-affinity IL-2Rβγ. ( d ) In vitro pSTAT5 assay in PBMCs shows that SHR-1916 exhibits better selectivity for the stimulation of CD8 + T and NK cells versus T reg cells compared to IL-2. ( e ) PBMC cytokine secretion assay shows that SHR-1916 retains the ability to promote IFNγ secretion while avoiding potential side effects associated with increasing levels of other cytokines. ( f ) In vivo mouse tumor model of CT-26 colon carcinoma demonstrates significant antitumor effects in the medium and high-dose groups, with tumor growth inhibition (TGI%) of 53.0% (p < 0.05) and 77.8% (p < 0.01), respectively. ( g ) In vivo mouse tumor model of A375 melanoma cells demonstrates significant antitumor effects in the three treatment groups, with tumor growth inhibition (TGI%) of 95.6% (p < 0.001), 91.8% (p < 0.001), and 89.1% (p < 0.01), respectively. ( h ) Pharmacokinetic study in rats SHR-1916 showed a significantly prolonged half-life, a lower clearance (Cl), and a longer mean residence time (MRT) compared to previously reported IL-2 data in rats.

Journal: Drug Design, Development and Therapy

Article Title: SHR-1916: A Novel PEGylated Interleukin-2 Analogue with Altered Cellular Selectivity and Improved Pharmacokinetic Profiles for Cancer Immunotherapy

doi: 10.2147/DDDT.S493011

Figure Lengend Snippet: Comprehensive study design and key findings of this research. ( a ) Binding affinity measurements by SPR show that SHR-1916 exhibits a significant IL-2Rβ-binding bias compared to IL-2 and reduced binding affinity to IL-2Rα. ( b ) and ( c ) In vitro cell proliferation assays using CTLL-2 and M07e cells demonstrate that SHR-1916 shows significantly lower proliferation efficiency in cell lines that express the high-affinity IL-2Rαβγ, while its impact on proliferation efficiency is less pronounced in cell lines that express the intermediate-affinity IL-2Rβγ. ( d ) In vitro pSTAT5 assay in PBMCs shows that SHR-1916 exhibits better selectivity for the stimulation of CD8 + T and NK cells versus T reg cells compared to IL-2. ( e ) PBMC cytokine secretion assay shows that SHR-1916 retains the ability to promote IFNγ secretion while avoiding potential side effects associated with increasing levels of other cytokines. ( f ) In vivo mouse tumor model of CT-26 colon carcinoma demonstrates significant antitumor effects in the medium and high-dose groups, with tumor growth inhibition (TGI%) of 53.0% (p < 0.05) and 77.8% (p < 0.01), respectively. ( g ) In vivo mouse tumor model of A375 melanoma cells demonstrates significant antitumor effects in the three treatment groups, with tumor growth inhibition (TGI%) of 95.6% (p < 0.001), 91.8% (p < 0.001), and 89.1% (p < 0.01), respectively. ( h ) Pharmacokinetic study in rats SHR-1916 showed a significantly prolonged half-life, a lower clearance (Cl), and a longer mean residence time (MRT) compared to previously reported IL-2 data in rats.

Article Snippet: The human CD25/IL-2Rα with a His-tag (Sino Biological, 10165-H08H) or CD122/IL-2Rβ with a His-tag (Sino Biological, 10696-H08B) was then immobilized.

Techniques: Binding Assay, In Vitro, In Vivo, Inhibition