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Adoptive immunotherapy against ovarian cancer.

ABSTRACT: The standard front-line therapy for epithelial ovarian cancer (EOC) is combination of debulking surgery and platinum-based chemotherapy. Nevertheless, the majority of patients experience disease recurrence. Although extensive efforts to find new therapeutic options, cancer cells invariably develop drug resistance and disease progression. New therapeutic strategies are needed to improve prognosis of patients with advanced EOC.Recently, several preclinical and clinical studies investigated feasibility and activity of adoptive immunotherapy in EOC. Our aim is to highlight prospective of adoptive immunotherapy in EOC, focusing on HLA-restricted Tumor Infiltrating Lymphocytes (TILs), and MHC-independent immune effectors such as natural killer (NK), and cytokine-induced killer (CIK). Adoptive cell therapy (ACT) has shown activity in several pre-clinical models. Available preclinical and clinical data suggest that adoptive cell therapy may provide the best benefit in settings of low tumor burden, minimal residual disease, or maintenance therapy. Further studies are needed to better define the optimal clinical setting.

SUBMITTER: Mittica G

PROVIDER: S-EPMC4869278 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Adoptive immunotherapy against ovarian cancer.

Mittica Gloria G Capellero Sonia S Genta Sofia S Cagnazzo Celeste C Aglietta Massimo M Sangiolo Dario D Valabrega Giorgio G

Journal of ovarian research 20160517 1

The standard front-line therapy for epithelial ovarian cancer (EOC) is combination of debulking surgery and platinum-based chemotherapy. Nevertheless, the majority of patients experience disease recurrence. Although extensive efforts to find new therapeutic options, cancer cells invariably develop drug resistance and disease progression. New therapeutic strategies are needed to improve prognosis of patients with advanced EOC.Recently, several preclinical and clinical studies investigated feasibi ...[more]

PMID: 27188274

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Project description:The generation of highly-reactive T lymphocytes against tumor-associated antigens remains an obstacle for effective adoptive immunotherapy of cancer. Recently, we found that microRNA-181a (miR-181a) acts as an intrinsic modulator of T cell antigen sensitivity in a transgenic T cell line in vitro. This molecule is part of a growing family of evolutionarily selected small interfering RNA that control gene expression at the posttranscriptional level by targeting messenger RNA (mRNA) for degradation or translational repression. Here, we explored the use of miR-181a to improve anti-tumor T cell responsiveness against weakly immunogenic tumor-associated antigens. We found that genetic engineering of T lymphocytes with miR-181a dramatically augmented the function of poorly responsive human tumor-infiltrating lymphocytes and TCR-engineered peripheral blood lymphocytes, resulting in potent anti-tumor reactivity. Furthermore, in a mouse model, miR-181a increased the function of self/tumor-specific CD8+ T cells enabling effective tumor destruction in the absence of vaccination or exogenous cytokines that were otherwise essential requirements and thus represents a significant advance over previous approaches. Although miRNAs have been previously shown to play critical functional roles in the development and function of vertebrate immune systems and pathogenesis of cancer, this report comprises the first use of a miRNA gene as tool in the treatment of disease. Keywords: cellular modification design For the 6 mouse samples the Operon Array-Ready Oligo Set (AROSâ¢) V 4.0 contains 35,852 longmer probes representing 25,000 genes and about 38,000 gene transcripts and also includes 380 controls platform was used and each sample was hybridized in duplicate. For the 6 human samples, the human cDNA microarray platform was used which consist of 17 k cDNA array included a combination from a RG_HsKG_031901 7 k clone set and 10,000 clones from the RG_Hs_seq_ver_070700 40 k clone set (Research Genetics, Huntsville, AL). The cDNA clones include 12,072 uniquely named genes, 875 duplicates of named genes.

Dataset Information

Adoptive immunotherapy against ovarian cancer.

Publications

Adoptive immunotherapy against ovarian cancer.

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