Ray Oomen

Publications (2)12.88 Total impact

• Article: Preclinical qualification of a new multi-antigen candidate vaccine for metastatic melanoma.

  Thorsten U Vogel, Lucian Visan, Belma Ljutic, Beata Gajewska, Judy Caterini, Danielle Salha, Tao Wen, Liwei He, Mark Parrington, Shi-Xian Cao, [......], Devender Sandhu, Nancy Scollard, Linong Zhang, Bill Bradley, Mei Tang, Corey Lovitt, Ray Oomen, Pamela Dunn, Jim Tartaglia, Neil L Berinstein
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  ABSTRACT: New therapies are urgently required for the treatment of patients with melanoma. Here we describe the generation and preclinical evaluation of 3 new recombinant ALVAC(2) poxviruses vCP2264, vCP2291, and vCP2292 for their ability to induce the desired cellular immune responses against the encoded melanoma-associated antigens. This was done either in HLA-A2/K transgenic mice or using in vitro antigen-presentation studies. These studies demonstrated that the vaccine was able to induce HLA-A*0201-restricted T-cell responses against gp100 and NY-ESO-1, detectable directly ex vivo, in HLA-A2/K-transgenic mice. The in vitro antigen presentation studies, in the absence of appropriate animal models, demonstrated that target cells infected with the vaccine construct were lysed by MAGE-1, MAGE-3 or MART-1 peptide-specific T cells. These data indicate that ALVAC(2)-encoded melanoma-associated antigens can be properly processed and presented to induce antigen-specific cytotoxic T-cell responses. To enhance the immunogenicity of the melanoma antigens, a TRIad of COstimulatory Molecules (TRICOM) were also cloned into all 3 vectors. Increased in vitro proliferation and IFN-γ production was observed with all ALVAC(2) poxviruses encoding TRICOM, confirming the immune-enhancing effect of the ALVAC-encoded TRICOM. These studies demonstrated that all components of the vaccine were functionally active and provide a rationale for moving this candidate vaccine to the clinic.
  Journal of immunotherapy (Hagerstown, Md.: 1997) 10/2010; 33(8):743-58. · 3.20 Impact Factor
• Source

  Available from: pnas.org

  Article: The gene associated with trichorhinophalangeal syndrome in humans is overexpressed in breast cancer.

  Laszlo Radvanyi, Devender Singh-Sandhu, Scott Gallichan, Corey Lovitt, Artur Pedyczak, Gustavo Mallo, Kurt Gish, Kevin Kwok, Wedad Hanna, Judith Zubovits, Jane Armes, Deon Venter, Jalil Hakimi, Jean Shortreed, Melinda Donovan, Mark Parrington, Pamela Dunn, Ray Oomen, James Tartaglia, Neil L Berinstein
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  ABSTRACT: A comprehensive differential gene expression screen on a panel of 54 breast tumors and >200 normal tissue samples using DNA microarrays revealed 15 genes specifically overexpressed in breast cancer. One of the most prevalent genes found was trichorhinophalangeal syndrome type 1 (TRPS-1), a gene previously shown to be associated with three rare autosomal dominant genetic disorders known as the trichorhinophalangeal syndromes. A number of corroborating methodologies, including in situ hybridization, e-Northern analysis using ORF EST (ORESTES) and Unigene EST abundance analysis, immunoblot and immunofluorescence analysis of breast tumor cell lines, and immunohistochemistry, confirmed the microarray findings. Immunohistochemistry analysis found TRPS-1 protein expressed in >90% of early- and late-stage breast cancer, including ductal carcinoma in situ and invasive ductal, lobular, and papillary carcinomas. The TRPS-1 gene is also immunogenic with processed and presented peptides activating T cells found after vaccination of HLA-A2.1 transgenic mouse. Human T cell lines from HLA-A*0201+ female donors exhibiting TRPS-1-specific cytotoxic T lymphocyte activity could also be generated.
  Proceedings of the National Academy of Sciences 08/2005; 102(31):11005-10. · 9.68 Impact Factor