123 research outputs found
Tularemia Outbreak, Bulgaria, 1997–2005
The 1997–2005 tularemia outbreak in Bulgaria affected 285 people. Ten strains were isolated from humans, a tick, a hare, and water. Amplified fragment length polymorphism typing of the present isolates and of the strain isolated in 1962 suggests that a new genetic variant caused the outbreak
A phase I trial of DNA vaccination with a plasmid expressing prostate-specific antigen in patients with hormone-refractory prostate cancer
Induction of viral and tumour specific CTL responses using antibody targeted HLA class I peptide complexes
The production of cytotoxic T cells with specificity for cancer cells is a rapidly evolving branch of cancer therapeutics. A variety of approaches aim to amplify anti-tumour cytotoxic T cell responses using purified peptides, tumour cell lysates or recombinant HLA/peptide complexes in differing antigen presenting systems. Using a two-step biotin-streptavidin antibody targeting system, recombinant HLA-class I/peptide complexes were attached to the surface of B cells via the anti-CD20 B9E9-scFvSA antibody-streptavidin fusion protein. Flow cytometry with a conformation dependant monoclonal antibody to HLA class I indicated that targeted HLA-class I/peptide complexes remain on the surface of B cells in culture for periods in excess of 72 h. PBMCs were stimulated in vitro for 8–14 days using the autologous B cells as antigen presenting cells. Following a single cycle of stimulation specific cytotoxic T cell responses to targeted HLA-A2 complexes containing the M1, BMLF1 and Melan A peptides could be demonstrated by tetramer staining and Cr release assays. With the HLA-A2/BMLF1 complex up to 2.99% of CD8+ve cells were tetramer positive producing 20% lysis (E : T 10 : 1) of CIR-A2 target cells in an in vitro cytotoxicity assay compared to baseline levels of 0.09% tetramer +ve and 2% lysis in the unstimulated population. PBMCs from a healthy donor treated with two cycles of stimulations with targeted HLA-A2/Melan A complexes, demonstrated expansion of the melanA tetramer +ve population from 0.03% to 1.4% producing 15% lysis of Melan A pulsed target cells. With further consideration to the key variables of HLA/peptide complex density, the ratio of stimulator to effector cells and optimum cytokine support, this system should offer an easy and effective method for the in vitro amplification of specific cytotoxic T cell responses and warrants development for the in vivo induction of cytotoxic T cell responses in cancer therapy
Prime–boost vaccination with plasmid and adenovirus gene vaccines control HER2/neu(+ )metastatic breast cancer in mice
INTRODUCTION: Once metastasis has occurred, the possibility of completely curing breast cancer is unlikely, particularly for the 30 to 40% of cancers overexpressing the gene for HER2/neu. A vaccine targeting p185, the protein product of the HER2/neu gene, could have therapeutic application by controlling the growth and metastasis of highly aggressive HER2/neu(+ )cells. The purpose of this study was to determine the effectiveness of two gene vaccines targeting HER2/neu in preventive and therapeutic tumor models. METHODS: The mouse breast cancer cell line A2L2, which expresses the gene for rat HER2/neu and hence p185, was injected into the mammary fat pad of mice as a model of solid tumor growth or was injected intravenously as a model of lung metastasis. SINCP-neu, a plasmid containing Sindbis virus genes and the gene for rat HER2/neu, and Adeno-neu, an E1,E2a-deleted adenovirus also containing the gene for rat HER2/neu, were tested as preventive and therapeutic vaccines. RESULTS: Vaccination with SINCP-neu or Adeno-neu before tumor challenge with A2L2 cells significantly inhibited the growth of the cells injected into the mammary fat or intravenously. Vaccination 2 days after tumor challenge with either vaccine was ineffective in both tumor models. However, therapeutic vaccination in a prime–boost protocol with SINCP-neu followed by Adeno-neu significantly prolonged the overall survival rate of mice injected intravenously with the tumor cells. Naive mice vaccinated using the same prime–boost protocol demonstrated a strong serum immunoglobulin G response and p185-specific cellular immunity, as shown by the results of ELISPOT (enzyme-linked immunospot) analysis for IFNγ. CONCLUSION: We report herein that vaccination of mice with a plasmid gene vaccine and an adenovirus gene vaccine, each containing the gene for HER2/neu, prevented growth of a HER2/neu-expressing breast cancer cell line injected into the mammary fat pad or intravenously. Sequential administration of the vaccines in a prime–boost protocol was therapeutically effective when tumor cells were injected intravenously before the vaccination. The vaccines induced high levels of both cellular and humoral immunity as determined by in vitro assessment. These findings indicate that clinical evaluation of these vaccines, particularly when used sequentially in a prime–boost protocol, is justified
DNA vaccination for prostate cancer: key concepts and considerations
While locally confined prostate cancer is associated with a low five year mortality rate, advanced or metastatic disease remains a major challenge for healthcare professionals to treat and is usually terminal. As such, there is a need for the development of new, efficacious therapies for prostate cancer. Immunotherapy represents a promising approach where the host’s immune system is harnessed to mount an anti-tumour effect, and the licensing of the first prostate cancer specific immunotherapy in 2010 has opened the door for other immunotherapies to gain regulatory approval. Among these strategies DNA vaccines are an attractive option in terms of their ability to elicit a highly specific, potent and wide-sweeping immune response. Several DNA vaccines have been tested for prostate cancer and while they have demonstrated a good safety profile they have faced problems with low efficacy and immunogenicity compared to other immunotherapeutic approaches. This review focuses on the positive aspects of DNA vaccines for prostate cancer that have been assessed in preclinical and clinical trials thus far and examines the key considerations that must be employed to improve the efficacy and immunogenicity of these vaccines
The use of specific anti-growth factor antibodies to abrogate the oncological consequences of transfusion in head & neck squamous cell carcinoma: an in vitro study
A Point of Honor: \u3cem\u3eDrengskapr in Þorsteins þáttr Stangarhǫggs\u3c/em\u3e
Þorsteins þáttr Stangarhǫggs, or “The Tale of Thorstein Staff-Struck” is an atypical piece of Norse short prose that likely originates from a mid-13th century oral tradition.1 Although the tale employs many of the common saga motifs, such as elaborate genealogies, and the plain prose of the genre, this perceived simplicity and objectivity is deceptive. Early 20th century scholars in particular, such as Vilhelm Grønbech, in their efforts to define the essence of the Icelandic Sagas, rightly identify numerous key themes in Icelandic literature but fail to acknowledge those themes as anything more than “aesthetic indulgence”.2 Such themes as honor, fate, and warrior heroism are likely more meaningful than Grønbech asserts in the sagas at large, but the way Þorsteins þáttr Stangarhǫggs and its indirect prequel, Vapnfirðingasaga, or The Saga of the Vapnfjord Men, wield the concepts of honor, masculinity, and warriorship directly challenges assertions in the vein of Grønbech. In these two stories, strong and respectable men seek parley; aggressive and warlike men meet disappointing ends; and heroes emerge from conflict without spilling a drop of each other’s blood. Þorsteins þáttr Stangarhǫggs diverts from common saga outcomes so sharply, that the notion that this eccentricity is meaningless seems nigh impossible. This þáttr, or tale, contains clear moral messages that reflect upon a society deeply wounded by cyclical violence and offers conscious and pragmatic alternatives to slaughter in defending one’s masculine honor
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