A phase I study of vaccination with NY-ESO-1f peptide mixed with Picibanil OK-432 and Montanide ISA-51 in patients with cancers expressing the NY-ESO-1 antigen

Department of Immunotherapeutics, University of Tokyo Hospital, Tokyo, Japan.
International Journal of Cancer (Impact Factor: 5.09). 12/2011; 129(12):2836-46. DOI: 10.1002/ijc.25955
Source: PubMed


We conducted a phase I clinical trial of a cancer vaccine using a 20-mer NY-ESO-1f peptide (NY-ESO-1 91-110) that includes multiple epitopes recognized by antibodies, and CD4 and CD8 T cells. Ten patients were immunized with 600 μg of NY-ESO-1f peptide mixed with 0.2 KE Picibanil OK-432 and 1.25 ml Montanide ISA-51. Primary end points of the study were safety and immune response. Subcutaneous injection of the NY-ESO-1f peptide vaccine was well tolerated. Vaccine-related adverse events observed were fever (Grade 1), injection-site reaction (Grade 1 or 2) and induration (Grade 2). Vaccination with the NY-ESO-1f peptide resulted in an increase or induction of NY-ESO-1 antibody responses in nine of ten patients. The sera reacted with recombinant NY-ESO-1 whole protein as well as the NY-ESO-1f peptide. An increase in CD4 and CD8 T cell responses was observed in nine of ten patients. Vaccine-induced CD4 and CD8 T cells responded to NY-ESO-1 91-108 in all patients with various HLA types with a less frequent response to neighboring peptides. The findings indicate that the 20-mer NY-ESO-1f peptide includes multiple epitopes recognized by CD4 and CD8 T cells with distinct specificity. Of ten patients, two with lung cancer and one with esophageal cancer showed stable disease. Our study shows that the NY-ESO-1f peptide vaccine was well tolerated and elicited humoral, CD4 and CD8 T cell responses in immunized patients.

Download full-text


Available from: Kazuhiro Kakimi, Oct 13, 2014
  • Source
    • "We have performed serial cancer vaccine clinical trials with NY-ESO-1 because of its strong immunogenicity and high specificity (Uenaka et al, 2007; Wada et al, 2008; Kakimi et al, 2011). The NY-ESO-1humoral immune response could be a reliable marker of the induction of immune response, as well as for predicting clinical responses in these trials. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: NY-ESO-1 antibodies are specifically observed in patients with NY-ESO-1-expressing tumours. We analysed whether the NY-ESO-1 humoral immune response is a useful tumour marker of gastric cancer. Methods: Sera from 363 gastric cancer patients were screened by enzyme-linked immunosorbent assay (ELISA) to detect NY-ESO-1 antibodies. Serial serum samples were obtained from 25 NY-ESO-1 antibody-positive patients, including 16 patients with curative resection and 9 patients who received chemotherapy alone. Results: NY-ESO-1 antibodies were detected in 3.4% of stage I, 4.4% of stage II, 25.3% of stage III, and 20.0% of stage IV patients. The frequency of antibody positivity increased with disease progression. When the NY-ESO-1 antibody was used in combination with carcinoembryonic antigen and CA19-9 to detect gastric cancer, information gains of 11.2% in stages III and IV, and 5.8% in all patients were observed. The NY-ESO-1 immune response levels of the patients without recurrence fell below the cutoff level after surgery. Two of the patients with recurrence displayed incomplete decreases. The nine patients who received chemotherapy alone continued to display NY-ESO-1 immune responses. Conclusion: When combined with conventional tumour markers, the NY-ESO-1 humoral immune response could be a useful tumour marker for detecting advanced gastric cancer and inferring the post-treatment tumour load in seropositive patients.
    Full-text · Article · Feb 2013 · British Journal of Cancer
  • Source
    • "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.
    Full-text · Article · Aug 2011 · European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Despite progress in the management of gastrointestinal malignancies, these diseases remain devastating maladies. Conventional treatment with chemotherapy and radiation is still only partially effective and highly toxic. In the era of increasing knowledge of the molecular biology of tumors and the interaction between the tumor and immune system, the development of targeted agents, including cancer vaccines, has emerged as a promising modality. In this paper, we discuss the principals of vaccine development, and we review most of the published trials on gastrointestinal cancer vaccines that have been conducted over the last decade. Many antigens and various treatment approaches have already been tested in colon, pancreatic, and other cancers. Some of these approaches have already shown some clinical benefit. In this paper, we discuss these different strategies and some of the future directions for targeting gastrointestinal malignancies with vaccines.
    Preview · Article · Aug 2011 · Gastroenterology and Hepatology
Show more