The cancer-testis antigen NY-ESO-1 is expressed by >40% of advanced epithelial ovarian cancers and is a promising immunotherapeutic target. In this study, we describe the effects of vaccination with the HLA-A*0201-restricted NY-ESO-1b peptide on patients with epithelial ovarian cancer in high-risk first remission.
After primary surgery and chemotherapy, high-risk epithelial ovarian cancer patients in first clinical remission received NY-ESO-1b peptide and Montanide every 3 weeks for five vaccinations. Tumor expression was evaluated by immunohistochemistry. Toxicity was monitored using National Cancer Institute Common Toxicity Criteria Scale Version 2. NY-ESO-1 specific humoral immunity (ELISA), T-cell immunity (tetramer and ELISPOT), and delayed-type hypersensitivity were assessed on weeks 0, 1, 4, 7, 10, 13, and 16.
Treatment-related adverse events included grade 1 fatigue, anemia, pruritus, myalgias, and hyperthyroidism and grade 2 hypothyroidism. There were no grade 3/grade 4 adverse events. Three of four patients (75%) with NY-ESO-1-positive tumor showed T-cell immunity by tetramer (0.6-9.5%) and ELISPOT (range, 35-260 spots). Four of five patients (80%) with NY-ESO-1-negative tumor showed T-cell immunity by tetramer (1.0-12.1%) and/or ELISPOT (range, 35-400 spots). With a median follow-up of 11.3 months, six of nine patients (67%) have recurred, with a median progression-free survival of 13 months (95% confidence interval, 11.2 months-not reached). Three of nine patients remain in complete clinical remission at 25, 38, and 52 months.
Vaccination of high-risk HLA-A*0201-positive epithelial ovarian cancer patients with NY-ESO-1b and Montanide has minimal toxicity and induces specific T-cell immunity in patients with both NY-ESO-1-positive and NY-ESO-1-negative tumors. Additional study is warranted.
"Active immunotherapy by vaccination based on peptides or cellular approaches were also evaluated. Clinically tested peptides include NY-ESO-1 [124,125], p53 , HER2-neu  and multiple constructed-peptides (HER2-neu/MAGE-A1/FRα  and MUC-1/carcinoembryonic antigen ). In addition, cell vaccines include DC pulsed with ARNm (FRα ), peptides (HER2-neu, MUC1 ), autologous tumor Ag  or whole tumor cell lysate . "
[Show abstract][Hide abstract] ABSTRACT: Epithelial ovarian cancer (EOC) is a significant cause of cancer-related mortality in women, and there has been no substantial decrease in the death rates due to EOC in the last three decades. Thus, basic knowledge regarding ovarian tumor cell biology is urgently needed to allow the development of innovative treatments for EOC. Traditionally, EOC has not been considered an immunogenic tumor, but there is evidence of an immune response to EOC in patients. Clinical data demonstrate that an antitumor immune response and immune evasion mechanisms are correlated with a better and lower survival, respectively, providing evidence for the immunoediting hypothesis in EOC. This review focuses on the immune response and immune suppression in EOC. The immunological roles of chemotherapy and surgery in EOC are also described. Finally, we detail pilot data supporting the efficiency of immunotherapy in the treatment of EOC and the emerging concept that immunomodulation aimed at counteracting the immunosuppressive microenvironment must be associated with immunotherapy strategies.
Journal of Translational Medicine 06/2013; 11(1):147. DOI:10.1186/1479-5876-11-147 · 3.93 Impact Factor
"Montanide has been tested in clinical trials (Diefenbach et al., 2008; Fourcade et al., 2008; Kakimi et al., 2011) and is the adjuvant component of the CIMAvax EGF therapeutic anticancer vaccine licensed in Latin America for use in adult patients with stage IIIB/ IV non-small-cell lung cancer (Rodriguez et al., 2010). In addition, Montanide in combination with CpG ODN and the recombinant NY-ESO-1 protein induced antigen-specific CD8 + T-cell responses in cancer patients, presumably via cross-presentation (Table 1) (Karbach et al., 2010; Valmori et al., 2007). "
[Show abstract][Hide abstract] ABSTRACT: Induction of CD8(+) T-cell responses is critical for the immunological control of a variety of diseases upon vaccination. Modern subunit vaccines are based on highly purified recombinant proteins. The high purity represents a major advancement in terms of vaccine safety compared to previous vaccination strategies with live attenuated or whole killed pathogens, but typically renders vaccine antigens poorly immunogenic and insufficient in mobilizing protective immunity. Adjuvants are therefore needed in vaccine formulations to enhance, direct and maintain the immune response to vaccine antigens. However, a weakness of many adjuvants is the lack of induction of CD8(+) T-cell responses against protein antigens, which are required for protection against challenging and difficult infectious diseases such as AIDS and for therapeutic cancer vaccination. Within the last decade, adjuvant systems that can induce CD8(+) T-cell responses have been developed and the first clinical trials demonstrating the clinical relevance of such formulations have been performed. This paper reviews the current status of lipid- and polymer-based particulate antigen delivery systems capable of stimulating CD8(+) T-cell immunity with special focus on mechanisms of priming and pharmaceutical requirements for optimal activation of cytotoxic T-lymphocytes that can kill virus-infected or abnormal (cancer) cells.
European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 08/2011; 45(4):482-91. DOI:10.1016/j.ejps.2011.08.016 · 3.35 Impact Factor
"In the current study, the immunological benefits of such immunization strategies, as well as the safety of these formulations, were further analysed in a non-human primate model. Two different adjuvants were used for vaccine formulation in this study; Montanide ISA 51 (w/o) is a proprietary adjuvant from Seppic (Paris, France) and has been used in a number of human studies [41-43]. CoVaccine HT™ (o/w) is also a proprietary adjuvant developed by Protherics Medicines Development Limited, a BTG International Group company, and has recently entered human trials . "
[Show abstract][Hide abstract] ABSTRACT: Increasing the breadth of the functional antibody response through immunization with Plasmodium falciparum apical membrane antigen 1 (PfAMA1) multi-allele vaccine formulations has been demonstrated in several rodent and rabbit studies. This study assesses the safety and immunogenicity of three PfAMA1 Diversity-Covering (DiCo) vaccine candidates formulated as an equimolar mixture (DiCo mix) in CoVaccine HT™ or Montanide ISA 51, as well as that of a PfAMA1-MSP1₁₉ fusion protein formulated in Montanide ISA 51.
Vaccine safety in rhesus macaques was monitored by animal behaviour observation and assessment of organ and systemic functions through clinical chemistry and haematology measurements. The immunogenicity of vaccine formulations was assessed by enzyme-linked immunosorbent assays and in vitro parasite growth inhibition assays with three culture-adapted P. falciparum strains.
These data show that both adjuvants were well tolerated with only transient changes in a few of the chemical and haematological parameters measured. DiCo mix formulated in CoVaccine HT™ proved immunologically and functionally superior to the same candidate formulated in Montanide ISA 51. Immunological data from the fusion protein candidate was however difficult to interpret as four out of six immunized animals were non-responsive for unknown reasons.
The study highlights the safety and immunological benefits of DiCo mix as a potential human vaccine against blood stage malaria, especially when formulated in CoVaccine HT™, and adds to the accumulating data on the specificity broadening effects of DiCo mix.
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