Seema Dubey

Kansas City VA Medical Center, Kansas City, Missouri, United States

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Publications (5)8.1 Total impact

  • The Journal of Urology 04/2014; 191(4):e503-e504. DOI:10.1016/j.juro.2014.02.1106 · 4.47 Impact Factor
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    11/2013; 1(Suppl 1):P55. DOI:10.1186/2051-1426-1-S1-P55
  • Seema Dubey · Peter VanVeldhuizen · Dev Karan ·
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    ABSTRACT: Prostate cancer is a significant health problem for men in the United States. While useful treatment modalities are available, their therapeutic efficacies are limited and severe side effects remain a concern. Alternatively, immunotherapy represents one of the most valuable treatments by inducing immune response targeting tumor cells. Sipuleucel-T is the only FDA approved immunotherapeutic agent for the treatment of patients with metastatic castration-resistant prostate cancer. Overall survival benefit with sipuleucel-T is modest, and the research field of cancer immunotherapy is continuously expanding. Numerous methods designed to induce tumor-specific immunity are at various developmental stages in clinical and preclinical studies. Among such modalities, the use of adenovirus vector (Ad) as an immunotherapy agent to deliver tumor-associated antigens is an attractive and versatile vector system. In this review, we describe the potential use of Ad-vector for prostate cancer immunotherapy.
    Current Cancer Therapy Reviews 11/2012; 8(4):264-270. DOI:10.2174/157339412804143087
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    ABSTRACT: Macrophage inhibitory cytokine-1 (MIC-1), also known as prostate-derived factor (PDF), is a molecule of the TGF-β superfamily and has been associated with the progression of various types of diseases including prostate cancer. Initially identified from activated macrophages, the MIC-1 gene may provide a potential link between inflammation and prostate cancer. In this context, we performed MIC-1 expression analysis using mouse prostate tissues to determine whether there was any correlation with age and inflammation. Reverse transcription PCR analysis on RNA samples isolated from prostate lobes from prostate-specific antigen transgenic mice of varying ages revealed that MIC-1 gene expression is extremely low to non-detectable in the prostate tissues obtained from young mice, while its expression increases in the prostate tissues harvested from elderly mice. Increased MIC-1 gene expression in the mouse prostate was found to be associated with an increased level of infiltrating lymphocytes. To confirm this observation, we showed that inflammation-associated cytokines (IL-1β and TNF-α) significantly upregulate the secretion of the MIC-1 protein in a human prostate cancer cell line (LNCaP cells), while cytokines IL-6 and granulocyte macrophage colony-stimulating factor were less effective. Taken together, these data indicated that inflammation-associated cytokines may play a critical role in the functional regulation of the MIC-1 gene in the early stages of prostate cancer development. More studies are required to understand the biological activity of MIC-1 gene regulation in the development and progression of prostate cancer.
    Oncology letters 05/2012; 3(5):1166-1170. DOI:10.3892/ol.2012.635 · 1.55 Impact Factor
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    ABSTRACT: We have previously shown that immunization with an adenovirus vector carrying an individual antigen induces antigen-specific CD8 T cells actively engaged in the destruction of tumor cells expressing the cognate antigen. In order to expand the range of antitumor responses beyond an individual antigen, we designed a recombinant adenovirus type 5 (rAd5) carrying a fusion construct of two full-length antigens. We used this adenovirus vector to test the concept that multiantigenic effector T cells could be generated simultaneously following a single immunization. To perform the rAd5 constructs, we selected a combination of prostate-specific antigen (PSA) and prostate stem cell antigen (PSCA) genes based on their restricted distribution within the prostate tissue and their association with the development and progression of prostate cancer. Immunization of mice with rAd5 vector carrying a fusion construct of PSA and PSCA (Ad5-PSA/PSCA) simultaneously induced the expansion of anti-PSA and anti-PSCA CD8 T cells, as measured by intracellular cytokine staining for IFN-γ. The antigen-specific T-cell responses that developed were efficient in eliminating the target cells expressing cognate antigens measured by an in vivo cytotoxic T-cell assay. The in vivo tumor growth study showed that immunization of mice with Ad5-PSA/PSCA vaccine induced strong antitumor immunity when challenged with mouse prostate tumor cell lines (RM11) expressing human PSA (RM11/PSA). To further analyze the impact on therapeutic efficacy of Ad5-PSA/PSCA vaccine against the tumor cells expressing PSA and PSCA (RM11-PSA/PSCA) antigens, we injected mice with Ad5-PSA/PSCA vaccine. The vaccine inhibited the growth of established tumors with 80% of the mice becoming tumor free. These data provide useful information that antigen-specific effector T cells can be generated simultaneously and that their additive antitumor effect has the potential to eliminate the growth of established tumors. Therefore, the immunotherapy approach of using the simultaneous targeting of dual antigens associated with prostate cancer may have important implications for human clinical trials.
    Immunotherapy 06/2011; 3(6):735-46. DOI:10.2217/imt.11.59 · 2.07 Impact Factor