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Phoebe Luo

Publications and source records attributed to Phoebe Luo.

5 recordsLinked to original sources
PubMed2005

Antigen epitope-expressing cytokines for DNA immunization.

Strategies to enhance the efficacy of DNA vaccination against malignancy remain to be established. In this study, a plasmid expressing a tumor antigen incorporated into the signal peptide of human IL-2 was tested as a DNA vaccine in a murine model system. Results showed that antigen-specific CTL responses were elicited by intramuscular injection of these plasmids. Importantly, compared with a minigene vector expressing the same epitope, the OVA epitope-incorporated, IL-2 expression plasmid vaccination was more effective in protecting mice from OVA-expressing tumor challenge. The improved efficacy appears to result from enhanced antigen presentation as well as the immunostimulatory activity of IL-2. This approach may provide new perspectives in designing cytokine-adjuvant DNA vaccines for clinical applications.

Animals↗
PubMed2005

Immuno-gene therapy of melanoma by tumor antigen epitope modified IFN-gamma.

Cytokine-based vaccines play a major part in tumor immuno-gene therapy. However, down-regulated antigen expression on tumor cells may diminish the immuno-potentiating aspects of cellular vaccines. In this study, we coexpressed a tumor antigen epitope with IFN-gamma in the same gene by replacing the IFN-gamma signal peptide with an antigen epitope-expressing signal peptide. We then investigated the effect of the antigen epitope-incorporated IFN-gamma on the immunotherapy of murine melanoma B16 tumors. Results showed that TRP-2 epitope-expressing IFN-gamma decreased B16 tumorigenicity and enhanced its immunogenicity after gene transfer. Protective immunity against wild type B16 tumors was induced by vaccination with IFN-gamma transiently gene-modified tumor cells. These data suggest that cellular vaccines engineered to express an antigen epitope within an immunostimulatory cytokine could potentiate the immunization effect.

Animals↗
PubMed2004

A novel inducible amplifier expression vector for high and controlled gene expression.

Safety and efficacy are both required for successful gene therapy. In this regard, our laboratory has created a novel expression system, pHi-Hot that combines inducible and amplifier strategies in one construct. In pHi-Hot, the first transcriptional unit contains an inducible heat shock protein (hsp70B) promoter controlling the expression of a transcriptional factor, Tat, which transactivates a second promoter, the HIV2 LTR, located downstream on the same construct. The second promoter drives the gene of interest. The magnitude of the amplified second gene expression can be regulated through manipulating the activity of the hsp promoter driving the Tat gene. Using the human interleukin-2 (IL-2) cytokine gene as the reporter gene, we demonstrated that moderate heat shock at 42 degrees C for 30 min, the pHi-Hot vector could achieve high gene expression levels while maintaining its inducibility. The induced IL-2 levels were 35- to 70-fold higher than achieved by using the hsp promoter alone, and 10- to 35-fold higher than achieved by using the CMV promoter. Using inducible and amplifier strategies, we can achieve high and controlled gene expression levels from a single construct. Finally, we discuss the advantages of using these strategies in developing new targeting and inducible vectors for genetic research and gene therapy.

Animals↗
PubMed2003

Enhanced tumor immunogenicity through coupling cytokine expression with antigen presentation.

The density of tumor antigen in conjunction with major histocompatibility complex (MHC) class I molecules on the cell surface affects cytotoxic T cell (CTL) function in an active antitumor immune response. Thus, methods to enhance antigen expression/presentation could augment the effect of cancer immune therapy. In the present study, we investigated the feasibility of modifying a cytokine signal peptide with a tumor antigenic epitope. We inserted the genes encoding the MHC class I-restricted antigenic epitope of chicken ovalbumin and tyrosinase-related protein 2 into the signal sequence of the interleukin-2 gene, replacing part of the signal sequence at different positions. Our results showed that these modified signal peptides still functioned, as indicated by cytokine secretion. The antigenic epitope within the modified signal peptide could be processed properly and presented on tumor cell surface. Tumor cells demonstrated enhanced immunogenicity as indicated by increased susceptibility to CTL lysis in vitro and decreased tumor grow in vivo after gene modification. These data provide potential perspectives in designing therapeutic or vaccine strategies in immuno-gene therapy of cancer.

Amino Acid Sequence↗