Immunotherapeutic approaches in prostate cancer: PROVENGE

ArticleinClinical advances in hematology & oncology: H&O 8(6):419-21 · June 2010with3 Reads
Source: PubMed
    • "Several studies have shown the potential of dendritic cells (DCs) as therapeutic vaccination against cancer. [1][2][3][4]However, only few vaccines have been approved for clinical use.[5] One of the challenges has been the establishment of efficient approaches that enhance the maturation profile of DCs and, in particular, presentation of antigens to cytotoxic T cells.[6] In fact, efficient induction of anti-tumor responses requires that DCs undergo proper maturation. "
    [Show abstract] [Hide abstract] ABSTRACT: Dendritic cells (DCs) hold promise for anti-cancer immunotherapy. However, clinically, their efficiency is limited and novel strategies to improve DC-mediated anti- tumor responses are needed. Human DCs display high content of sialic acids, which inhibits their maturation and co-stimulation capacity. Here, we aimed to understand whether exogenous desialylation of DCs improves their anti-tumor immunity. Compared to fully sialylated DCs, desialylated human DCs loaded with tumor-antigens showed enhanced ability to induce autologous T cells to proliferate, to secrete Th1 cytokines, and to specifically induce tumor cell apoptosis. Desialylated DCs showed an increased expression of MHC-I and -II, co-stimulatory molecules and an augmented secretion of IL-12. Desialylated HLA-A*02:01 DCs pulsed with gp100 peptides displayed enhanced peptide presentation through MHC-I, resulting in higher activation of gp100280–288 specific CD8+ cytotoxic T cells. Desialylated murine DCs also exhibited increased MHC and co-stimulatory molecules and higher antigen cross-presentation via MHC-I. These DCs showed higher ability to activate antigen-specific CD4+ and CD8+ T cells, and to specifically induce tumor cell apoptosis. Collectively, our data demonstrates that desialylation improves DCs’ ability to elicit T cell-mediated anti- tumor activity, due to increased MHC-I expression and higher antigen presentation via MHC-I. Sialidase treatment of DCs may represent a technology to improve the efficacy of antigen loaded-DC-based vaccines for anti-cancer immunotherapy.
    Full-text · Article · Jun 2016 · Oncotarget
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    • "When NK cells and T-cells infiltrate the prostate cancer microenvironment, they are exposed to potent immunosuppressive mechanisms that render them unable to kill tumour cells. Regulatory T-cells are frequently observed in prostate tumours with a CD4 + CD25 + FOXP3 + (FOXP3 is forkhead box P3) phenotype or a novel CD8 + FOXP3 + phenotype [9]; it is observed that these latter suppressive cells arise by the conversion of CD8 + effector cells when they enter the prostate tumour microenvironment [10]. Where cells are not converted into a suppressive phenotype, they can still be rendered anergic. "
    [Show abstract] [Hide abstract] ABSTRACT: Prostate adenocarcinoma is present in over 80% of men over the age of 80 and is by far the most common cancer of men. Although radical prostatectomy is curative in early disease, the risks of incontinence and impotence can affect the quality of life of patients. Early intervention with localized immunotherapy represents a potential solution as lymphocyte infiltration does occur in prostate cancer lesions, and immunotherapy with dendritic cell vaccines can significantly increase survival in late stage disease. However, lymphocytic infiltrates in the cancerous prostates have an anergic character arising from the suppressive effects of the microenvironment resulting from a conversion of effector cells into regulatory T-cells. Although TGFβ (transforming growth factor β) and IL-10 (interleukin-10) are known to be strong suppressor molecules associated with prostate cancer, they are among many possible suppressive factors. We discuss the possible role of alternative suppressor molecules, including the WAP (whey acidic protein) homologue ps20 that is expressed on prostate stroma and other WAP domain-containing proteins in the immunosuppressive prostate cancer milieu and discuss novel immunotherapeutic strategies to combat this disease.
    Full-text · Article · Oct 2011
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    • "When NK cells and T-cells infiltrate the prostate cancer microenvironment, they are exposed to potent immunosuppressive mechanisms that render them unable to kill tumour cells. Regulatory T-cells are frequently observed in prostate tumours with a CD4 + CD25 + FOXP3 + (FOXP3 is forkhead box P3) phenotype or a novel CD8 + FOXP3 + phenotype [9]; it is observed that these latter suppressive cells arise by the conversion of CD8 + effector cells when they enter the prostate tumour microenvironment [10]. Where cells are not converted into a suppressive phenotype, they can still be rendered anergic. "
    [Show abstract] [Hide abstract] ABSTRACT: Prostate adenocarcinoma is present in over 80% of men over the age of 80 and is by far the most common cancer of men. Although radical prostatectomy is curative in early disease, the risks of incontinence and impotence can affect the quality of life of patients. Early intervention with localized immunotherapy represents a potential solution as lymphocyte infiltration does occur in prostate cancer lesions, and immunotherapy with dendritic cell vaccines can significantly increase survival in late stage disease. However, lymphocytic infiltrates in the cancerous prostates have an anergic character arising from the suppressive effects of the microenvironment resulting from a conversion of effector cells into regulatory T-cells. Although TGFβ (transforming growth factor β) and IL-10 (interleukin-10) are known to be strong suppressor molecules associated with prostate cancer, they are among many possible suppressive factors. We discuss the possible role of alternative suppressor molecules, including the WAP (whey acidic protein) homologue ps20 that is expressed on prostate stroma and other WAP domain-containing proteins in the immunosuppressive prostate cancer milieu and discuss novel immunotherapeutic strategies to combat this disease.
    Full-text · Article · Oct 2011 · Biochemical Society Transactions
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