OX40 agonists for cancer treatment: a patent review

Cebada, Jorge; Pérez-Santos, Martín; Bandala, Cindy; Lara‐Padilla, Eleazar; Herrera‐Camacho, Irma; Rosas-Murrieta, Nora Hilda; Peña, Lourdes Millán-Pérez; Monjaraz, Eduardo; Flores, Amira; Anaya-Ruı́z, Maricruz

doi:10.1080/13543776.2021.1825688

Cited by 10 publications

(8 citation statements)

References 34 publications

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“…These paradoxical results could be explained by heterogeneous TME and homeostatic regulation of Tregs [ 31 ]. Encouragingly, the latest evidence reinforced the notion that immunotherapy with TNFRSF4 agonists would trigger a new trend in cancer therapies [ 32 ]. For example, TNFRSF4 stimulation plus a CTLA-4 blockade functioned as a potential therapeutic strategy to eradicate disseminated tumors [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of TNFRSF4 as a high-profile biomarker for prognosis and immunomodulation in endometrial carcinoma

Feng

et al. 2022

BMC Cancer

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Background The interaction between tumor microenvironment (TME) and tumors offers various targets in mounting anti-tumor immunotherapies. However, the prognostic biomarkers in endometrial carcinoma (EC) are still limited. Here, we aimed to analyze the TME features and identify novel prognostic biomarkers for EC. Methods ESTIMATE, CIBERSORT, protein-protein interaction (PPI) network, univariate and multivariate Cox regression, and functional enrichment analysis were performed to identify immune- and survival-related hub genes as well as possible molecular mechanisms. The limma package and deconvolution algorithm were adopted to estimate the abundance of tumor-infiltrating immune cells (TICs) and their relationship with the target gene. In the validation section, tissue microarrays (TMAs) of EC and multiplex immunohistochemistry (m-IHC) were evaluated to validate the expression of TNFRSF4, and its correlation with immune markers, including CD4, CD8, and FOXP3. Besides, the receiver operating characteristic (ROC) curve was plotted to determine the diagnostic performance of TNFRSF4, CD4, CD8, and FOXP3 in EC. Results Two genes, TNFRSF4 and S1PR4, were screened out from 386 intersection differential expression genes (DEGs) shared by ImmuneScore and StromalScore in EC. Highlighted by TNFRSF4, we found that it was not only positively correlated with the TICs (mainly CD4+ T cells, CD8+ T cells, and Tregs) but significantly related to the prognosis in patients of EC, both verified by data from The Cancer Genome Altas (TCGA)-EC database and clinical samples. At the same time, the expression trend of TNFRSF4 was further confirmed by an integrated meta-analysis based on six microarrays from the Gene Expression Omnibus database (GEO). Conclusions Collectively, TNFRSF4, a previously unrecognized key player in EC, could serve as a potential biomarker for prognosis prediction and immunomodulation of EC.

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Section: Discussionmentioning

confidence: 99%

Identification and validation of TNFRSF4 as a high-profile biomarker for prognosis and immunomodulation in endometrial carcinoma

Feng

et al. 2022

BMC Cancer

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“…These paradoxical results could be explained by heterogeneous TME and homeostatic regulation of Tregs [26] . Encouragingly, the latest evidence reinforced the notion that immunotherapy with TNFRSF4 agonists would trigger a new trend in cancer therapies [27] . For example, TNFRSF4 stimulation plus a CTLA-4 blockade functioned as a potential therapeutic strategy to eradicate disseminated tumors [28] .…”

Section: Discussionmentioning

confidence: 97%

Identification and Validation of TNFRSF4 as a High-profile Biomarker for Prognosis and Immunomodulation in Endometrial Carcinoma

Feng

et al. 2022

Preprint

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Background: The interaction between tumor microenvironment (TME) and tumors offers various targets in mounting anti-tumor immunotherapies. However, the diagnostic and prognostic biomarkers in endometrial carcinoma (EC) are still limited. Here, we aimed to analyze the TME features and identify novel prognostic biomarkers for EC. Methods: ESTIMATE, CIBERSORT, protein-protein interaction (PPI) network, univariate Cox regression, and functional enrichment analysis were performed to identify immune- and survival-related hub genes as well as possible molecular mechanisms. The limma package and deconvolution algorithm were adopted to estimate the abundance of tumor-infiltrating immune cells (TICs) and their relationship with the target gene. In validation section, tissue microarrays (TMAs) of EC and multiplex immunohistochemistry (m-IHC) were evaluated to validate the expression of TNFRSF4, and its correlation with immune markers, including CD4, CD8, and FOXP3. The receiver operating characteristic (ROC) curve was used to determine the efficacy of TNFRSF4, CD4, CD8, and FOXP3 in diagnosing EC. Results: Two genes, TNFRSF4 and S1PR4, were screened out from 386 intersection differential expression genes (DEGs) shared by ImmuneScore and StromalScore in EC. Highlighted by TNFRSF4, we found that it was not only positively correlated with the TICs (mainly CD4+ T cells, CD8+ T cells, and Tregs) but significantly related to diagnosis and prognosis in patients of EC, both verified by data from the TCGA database and clinical samples. At the same time, the expression trend of TNFRSF4 was further confirmed by an integrated meta-analysis based on six microarrays from the Gene Expression Omnibus database (GEO). Conclusions: Collectively, TNFRSF4 could serve as a high-profile biomarker to robustly predict immune microenvironment, clinical diagnosis, and prognosis for EC.

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“…Antibodies that block immune checkpoints, such as CTLA‐4 antibody and PD‐1 / PD‐L1 antibody, have made breakthrough in the past decades 19‐21 . However, agonistic antibodies against costimulatory receptors (such as OX40) have not achieved good efficacy in early clinical trials 22 . In the phase IB trial of Genentech's OX40 agonist MOXR0916, combined with PDL1 inhibitor atezolizumab, only 2 of 51 (4%) patients had a partial response.…”

Section: Discussionmentioning

confidence: 99%

“… 19 , 20 , 21 However, agonistic antibodies against costimulatory receptors (such as OX40) have not achieved good efficacy in early clinical trials. 22 In the phase IB trial of Genentech's OX40 agonist MOXR0916, combined with PDL1 inhibitor atezolizumab, only 2 of 51 (4%) patients had a partial response. Genentech terminated the clinical trial of OX40 agonist in May 2019.…”

Section: Discussionmentioning

confidence: 99%

Tumor eradicated by combination of imiquimod and OX40 agonist for in situ vaccination

Chu

Qian

et al. 2021

Cancer Science

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Various cancer vaccines have been developed to generate and amplify antigen‐specific T cell responses against malignancy. Among them, in situ vaccination is one of the most practical types as it can trigger immune responses without previous antigen identification. Here we reported a novel in situ vaccine by intratumoral injection of imiquimod and OX40 agonist. In mice bearing hepatic carcinoma, both the injected tumor and the noninjected tumor in the distant lesion of the same mice were suppressed after vaccination. Further studies found that this in situ vaccine triggered systemic tumor‐specific responses, with one‐fold increase of effector memory T cells properties and stronger toxicity of lymphocytes in spleen. Besides, we found that imiquimod upregulated the expression of OX40 on CD4+ T cells and thus enhanced the effectiveness of OX40 agonist. Five immune‐positive‐related pathways were activated after vaccination. This in situ vaccine caused little harm to normal organs and provided long‐term protection against the same syngeneic tumor rechallenge. Due to its effectiveness, feasibility and safety, this strategy could potentially be applied to various types of late‐stage solid tumors and worthy of further clinical research.

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OX40 agonists for cancer treatment: a patent review

Cited by 10 publications

References 34 publications

Identification and validation of TNFRSF4 as a high-profile biomarker for prognosis and immunomodulation in endometrial carcinoma

Identification and validation of TNFRSF4 as a high-profile biomarker for prognosis and immunomodulation in endometrial carcinoma

Identification and Validation of TNFRSF4 as a High-profile Biomarker for Prognosis and Immunomodulation in Endometrial Carcinoma

Tumor eradicated by combination of imiquimod and OX40 agonist for in situ vaccination

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