&lt;p&gt;Application Of Adoptive Immunotherapy In Ovarian Cancer&lt;/p&gt;

Yang, Siyu; Yin, Xiaojiao; Ye, Ying; Wang, Siqing

doi:10.2147/ott.s221773

Cited by 8 publications

(5 citation statements)

References 115 publications

(113 reference statements)

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“…Immunotherapy can be classified into two categories: (1) active immunotherapy (e.g., cancer vaccines); and (2) passive or adoptive immunotherapy, such as monoclonal antibodies and adoptive cell therapies (ACT). As cellular immunity plays an important role in antitumor immunity, ACT has become a powerful treatment strategy for cancers, including ovarian cancer (9,10). ACT of dendritic cells (DCs), the main antigen presenting cells, together with cytokine induced killer cells (CIKs), has shown great potential to prevent tumor recurrence, increase progression-free survival (PFS) rates, and improve the quality of life of cancer patients (11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Preliminary Safety and Potential Effect of 6B11-OCIK Adoptive Cell Therapy Against Platinum-Resistant Recurrent or Refractory Ovarian Cancer

Cheng

Wang

et al. 2021

Front. Immunol.

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Ovarian cancer is a leading cause of death among gynecological malignancies, and novel therapies are urgently needed. Here we report preliminary findings on the potential safety and efficacy of 6B11-OCIK, an adoptive cell therapy of autologous T cells induced by the humanized anti-idiotypic antibody 6B11 minibody plus dendritic cells and cytokines, against platinum-resistant recurrent or refractory ovarian cancer in three patients. We found that 6B11-OCIK treatment was safe and well tolerated after five cycles of intravenous infusion with an initial dose of 1–2×109 cells and a dose-climbing strategy. Hemoglobin, platelets, white cell count, creatinine or liver enzyme values, coagulation function, kidney and heart function were not significantly affected over the duration of therapy. Two of the three enrolled patients showed potentially drug-related grade 1 and 2 weakness, and no other adverse events were observed. Of the three enrolled patients, one had stable disease and two showed disease progression. The patient with favorable clinical efficacy had better immune response as measured by 6B11-OCIK proliferation capacity, activation ability of CD3+CD8+ tumor-specific cytotoxic T lymphocytes and CD3+CD56+ cytokine-induced killer cells, and tumor cell killing efficiency. Changes in circulating tumor cells after treatment were consistent with serum level CA125 in the patient with stable disease (both decreased), while differences were observed in the two patients with disease progression (increased CA125 in both and decreased CTC in the patient with better immune response), suggesting that variation of circulating tumor cells was more consistent with immune response and reflected efficacy directly. This preliminary study suggested that autologous 6B11-OCIK treatment was safe and had potential clinical efficacy against ovarian cancer. Patients with better immune response had more favorable efficacy. In addition to imaging, CA125 and immunophenotypes, CTC monitoring may represent a potential indicator of immunotherapy response.

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Section: Introductionmentioning

confidence: 99%

Preliminary Safety and Potential Effect of 6B11-OCIK Adoptive Cell Therapy Against Platinum-Resistant Recurrent or Refractory Ovarian Cancer

Cheng

Wang

et al. 2021

Front. Immunol.

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“…Ovarian cancer is an immunogenic tumor that can be recognized and attacked by the immune system. The accumulation of TILs in ovarian cancer microenvironment is related to prolonged OS of the patients, while immune escape events are associated with poor prognosis [51,52]. In this study, the correlation between UBE2T expression and the levels of in ltrating immune cells was analyzed by using the TISIDB-OV database.…”

Section: Discussionmentioning

confidence: 99%

Increased Expression of UBE2T Predicting Poor Survival of Epithelial Ovarian Cancer: Based on Comprehensive Analysis of UBE2s, Clinical Samples, and the GEO Database

Zou

et al. 2021

DNA and Cell Biology

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Background Ubiquitin-conjugating enzymes E2 (UBE2) have been reported in the microenvironment of various malignant tumors, but their correlation with ovarian cancer remains elusive.Methods: The Oncomine, GEPIA, Kaplan-Meier Plotter, cBioPortal, and STRING databases were used to systematically analyze the expression pattern, prognostic value, genetic variation, and biological function of 12 members of the UBE2 gene family in ovarian cancer. UBE2T exhibited a strong correlation with ovarian cancer and was thus further examined. Gene set enrichment analysis (GSEA), as well as analyses of function and pathway enrichment, somatic mutations, copy number variation, and methylation were performed, and the correlation with immune cell in ltration was examined to explore the mechanism underlying aberrant UBE2T expression. Finally, the expression and prognostic value of UBE2T in ovarian cancer were veri ed by immunohistochemical evaluation of 131 clinical ovarian samples and the Gene Expression Omnibus (GEO) database (GSE51088, GSE73614, and GSE63885 datasets) analysis.Results: The mRNA levels of UBE2C, UBE2N, UBE2S, and UBE2T were signi cantly upregulated in ovarian cancer compared with those in normal ovarian tissue. In patients with ovarian serous carcinoma, UBE2A, UBE2B, UBE2C, UBE2G, UBE2R2 and UBE2T upregulation were associated with poor overall survival. Moreover, UBE2A, UBE2N, UBE2R2 and UBE2T upregulation and UBE2G downregulation were associated with poor progression-free survival. Immunohistochemistry revealed that UBE2T was signi cantly upregulated in ovarian malignant tumors compared with that in borderline tumors, benign tumors, and normal ovarian tissues, and its high expression was associated with poor prognosis. The Cox model showed that UBE2T upregulation was an independent risk factor affecting the prognosis of ovarian cancer (hazard ratio: 4.095, P=0.029). The above results were veri ed in the GEO database. In addition, UBE2T was associated with speci c immune cells and mainly involved in cell cycle-related events. Genomic analysis showed that TP53 and TTN mutations were associated with UBE2T expression. Gene copy number ampli cation and hypomethylation may be responsible for UBE2T upregulation in ovarian cancer.Conclusions: UBE2 family members may play a role in the development of ovarian cancer. Speci cally, UBE2T could serve as a new prognostic marker and therapeutic target for this disease.

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“…OC is an immunogenic tumor that can be recognized and attacked by the immune system. The accumulation of TILs in OC microenvironment is related to prolonged OS of the patients, while immune escape events are associated with poor prognosis [64,65]. In this study, the correlation between UBE2T expression and the levels of in ltrating immune cells was analyzed by using the TISIDB-OV database.…”

Section: Discussionmentioning

confidence: 99%

Increased expression of UBE2T predicting poor survival of ovarian cancer: based on comprehensive analysis of UBE2s, clinical samples and the GEO database

Zou

et al. 2020

Preprint

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Background： Ubiquitin-conjugating enzymes E2 (UBE2) have been reported in the microenvironment of various malignant tumors, but their correlation with ovarian cancer remains elusive.Methods: The Oncomine, GEPIA, Kaplan-Meier Plotter, cBioPortal, and STRING databases were used to systematically analyze the expression pattern, prognostic value, genetic variation, and biological function of 12 members of the UBE2 gene family in ovarian cancer. UBE2T exhibited the greatest correlation with ovarian cancer and was thus further examined. Gene set enrichment analysis (GSEA), as well as analyses of function and pathway enrichment, somatic mutations, copy number variation, and methylation were performed, and the correlation with immune cell infiltration was examined to explore the mechanism underlying aberrant UBE2T expression. Finally, the expression and prognostic value of UBE2T in ovarian cancer were verified by immunohistochemical evaluation of 131 clinical ovarian samples and the Gene Expression Omnibus (GEO) database (GSE51088, GSE73614, and GSE63885 datasets) analysis.Results: The mRNA levels of UBE2C , UBE2N , UBE2S , and UBE2T were significantly upregulated in ovarian cancer compared with those in normal ovarian tissue. In patients with ovarian serous carcinoma, UBE2A , UBE2B , UBE2C , UBE2G , and UBE2T upregulation and UBE2R2 downregulation were associated with poor overall survival. Moreover, UBE2A , UBE2N , and UBE2T upregulation and UBE2G and UBE2R2 downregulation were associated with poor progression-free survival. Immunohistochemistry revealed that UBE2T was significantly upregulated in ovarian malignant tumors compared with that in borderline tumors, benign tumors, and normal ovarian tissues, and its high expression was associated with poor prognosis. The Cox model showed that UBE2T upregulation was an independent risk factor affecting the prognosis of ovarian cancer (hazard ratio: 4.095, P= 0.029). The above results were verified in the GEO database. In addition, UBE2T was associated with specific immune cells and mainly involved in cell cycle-related events. Genomic analysis showed that TP53 and TTN mutations were associated with UBE2T expression. Gene copy number amplification and hypomethylation may be responsible for UBE2T upregulation in ovarian cancer.Conclusions: UBE2 family members may play a role in the development of ovarian cancer. Specifically, UBE2T could serve as a new prognostic marker and therapeutic target for this disease.

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<p>Application Of Adoptive Immunotherapy In Ovarian Cancer</p>

Cited by 8 publications

References 115 publications

Preliminary Safety and Potential Effect of 6B11-OCIK Adoptive Cell Therapy Against Platinum-Resistant Recurrent or Refractory Ovarian Cancer

Preliminary Safety and Potential Effect of 6B11-OCIK Adoptive Cell Therapy Against Platinum-Resistant Recurrent or Refractory Ovarian Cancer

Increased Expression of UBE2T Predicting Poor Survival of Epithelial Ovarian Cancer: Based on Comprehensive Analysis of UBE2s, Clinical Samples, and the GEO Database

Increased expression of UBE2T predicting poor survival of ovarian cancer: based on comprehensive analysis of UBE2s, clinical samples and the GEO database

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