Conjugate of ibrutinib with a TLR7 agonist suppresses melanoma progression and enhances antitumor immunity

Ren, Sumei; Wang, Xiaodong; Jin, Guangyi

doi:10.7150/ijbs.64094

Cited by 6 publications

(8 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was discovered that chemically coupling ibrutinib with TLR7 receptor agonists to produce novel immune-targeting complexes called GY161 increased the levels of CD8 + T cells in spleen and tumor in vivo. GY161 inhibited the growth of B16 melanoma cell-derived tumors and prolonged the survival time of mice [51].…”

Section: Discussionmentioning

confidence: 96%

Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma

Xing

Jia

Han

2022

Preprint

View full text Add to dashboard Cite

Background Cutaneous melanoma (CM), a kind of skin cancer with a high rate of advanced mortality, exhibits a wide variety of driver and transmitter gene alterations in the immunological tumor microenvironment (TME) associated with tumor cell survival and proliferation. Methods We analyzed the immunological infiltration of TME cells in normal and malignant tissues using 469 CM and 556 normal skin samples. We used a single sample gene set enrichment assay (ssGSEA) to quantify the relative abundance of 28 cells, developed a riskScore prognostic model using the LASSO COX regression model, and performed small molecule drug screening and molecular docking validation, which was finally validated using qRT-PCR and IHC. Results We developed a prognosis model around seven essential protective genes for the first time, dramatically elevated in tumor tissues, as did immune cell infiltration. The results of multivariate Cox regression demonstrated that riskScore is an independent and robust prognostic indicator, and its predictive usefulness in immunotherapy was verified. Additionally, we identified Gabapentin as a possible small molecule therapeutic for CM. Conclusions A riskScore model was developed in this work to analyze patient prognosis, TME cell infiltration features, and treatment responsiveness. The development of this model aid in predicting patient response to immunotherapy, but it also has significant implications for the development of novel immunotherapeutic agents and the promotion of tailored treatment regimens.

show abstract

Section: Discussionmentioning

confidence: 96%

Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma

Xing

Jia

Han

2022

Preprint

View full text Add to dashboard Cite

show abstract

“… 103 have developed dual CD39/ALK inhibitors, and Ren et al. 86 designed dual-acting TLR7/BTK modulators by chemically conjugating a TLR7 agonist to ibrutinib.…”

Section: Discussionmentioning

confidence: 99%

“…Compound 31 (GY161): Ren et al. 86 designed a novel TLR7/BTK dual-targeting compound 31 by chemically conjugating a TLR7 agonist to ibrutinib (BTK inhibitor). In vitro , 31 activated TLR7 (EC 50 = 1.86 μmol/L) and promoted the maturation of DCs.…”

Section: Small Molecule Immunomodulators Targeting the Innate Immune ...mentioning

confidence: 99%

Small molecule-based immunomodulators for cancer therapy

Yang

Cheng

et al. 2022

Acta Pharmaceutica Sinica B

View full text Add to dashboard Cite

“…Chemically coupling ibrutinib with TLR7 receptor agonists to produce novel immune-targeting complexes termed GY161 increased CD8 + T cell levels in spleen and tumor in vivo . GY161 inhibited the growth of B16 melanoma cell-derived tumors and prolonged the survival time of mice ( 59 ).…”

Section: Discussionmentioning

confidence: 99%

Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma

Xing

Jia

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

BackgroundCutaneous melanoma (CM), a kind of skin cancer with a high rate of advanced mortality, exhibits a wide variety of driver and transmitter gene alterations in the immunological tumor microenvironment (TME) associated with tumor cell survival and proliferation.MethodsWe analyzed the immunological infiltration of TME cells in normal and malignant tissues using 469 CM and 556 normal skin samples. We used a single sample gene set enrichment assay (ssGSEA) to quantify the relative abundance of 28 cells, then used the LASSO COX regression model to develop a riskScore prognostic model, followed by a small molecule drug screening and molecular docking validation, which was then validated using qRT-PCR and IHC.ResultsWe developed a prognosis model around seven essential protective genes for the first time, dramatically elevated in tumor tissues, as did immune cell infiltration. Multivariate Cox regression results indicated that riskScore is an independent and robust prognostic indicator, and its predictive value in immunotherapy was verified. Additionally, we identified Gabapentin as a possible small molecule therapeutic for CM.ConclusionsA riskScore model was developed in this work to analyze patient prognosis, TME cell infiltration features, and treatment responsiveness. The development of this model not only aids in predicting patient response to immunotherapy but also has significant implications for the development of novel immunotherapeutic agents and the promotion of tailored treatment regimens.

show abstract

Conjugate of ibrutinib with a TLR7 agonist suppresses melanoma progression and enhances antitumor immunity

Cited by 6 publications

References 29 publications

Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma

Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma

Small molecule-based immunomodulators for cancer therapy

Construction of immunotherapy-related prognostic gene signature and small molecule drug prediction for cutaneous melanoma

Contact Info

Product

Resources

About