A phase 1 clinical trial of NY-ESO-1 protein formulated with immunostimulatory complexes (ISCOM® adjuvant) in patients with minimal residual disease (2003)

Spontaneous antibody and cellular immune responses against the cancer testis antigen NY-ESO-1 occur in a subset of patients with NY-ESO-1 expressing tumors. NY-ESO-1 specific immune responses to injected HLA A2-restricted peptides of NY-ESO-1 have also been reported in patients with spontaneous NY-ESO-1 immunity. Furthermore, a number of Class-II epitopes to NY-ESO-1 presented on HLA DP4, DR53 and DR4 have been identified. The potential to stimulate both CD8+ and CD4+ T-cell responses following vaccination with full-length NY-ESO-1 protein formulated with ISCOM® (ImmunoStimulating COMplexeS, CSL Ltd, Australia) adjuvant was pursued in a Phase 1 study. The ISCOM® adjuvant is saponin-based and has been shown to stimulate antibody responses and induce T helper cell as well as cytotoxic T lymphocyte responses in a variety of animal models and human clinical trials. The objectives of the current study were to evaluate the safety and immunogenicity of an NY-ESO-1 ISCOM® vaccine. Forty-six (46) patients with minimal residual disease and tumors that expressed NY-ESO-1 antigen by immunohistochemistry and/or RT-PCR were evaluated in the study. Patients received NY-ESO-1 ISCOM® or protein alone, administered IM on three occasions at monthly intervals. NY-ESO-1 ISCOM® protein doses were: 10 µg (n = 3), 30 µg (n = 3), and 100 µg (n = 20). A further 20 patients received 100 µg NY-ESO-1 protein alone. All patients except 10 in each of the 100 µg groups were HLA-A2 positive, and 2 patients in each group of 10 received placebo. Patients were evaluated for toxicity each week. Immune function was assayed in all patients by Delayed Type Hypersensitivity (DTH) to NY-ESO-1 protein alone and by NY-ESO-1 antibody titre (ELISA). In HLA-A2 patients the number of reactive NY-ESO-1 CD8+ T cells was measured by HLA-A2 tetramers and by Cytospot assay for gamma-interferon production. Results: Grade 3 injection site pain occurred in three patients who received 100 µg. Grade 2 injection site pain, flu-like symptoms, fever and malaise were also noted, otherwise the vaccine was generally very well tolerated. At the 100 µg dose of the NY-ESO-1 ISCOM® vaccine, enhanced DTH reactions (up to 60 mm redness and 25 mm induration) over baseline occurred. Antibody titres were significantly higher (>1:100,000) in patients immunized with ISCOM® formulation than with NY-ESO-1 protein alone. CD8+ cellular immune responses were observed in one of three NY-ESO-1 ISCOM® patients at the 10 µg dose (a patient with prior antibody response), and otherwise at the 100 µg dose, primarily in patients who received the vaccine with adjuvant. There was a good correlation between tetramer and cytospot findings but little or no correlation between DTH and the monitored ESO1b-specific CD8+ T-cell responses. One patient has shown evidence of a response to a new peptide epitope presented on HLA DR2. This patient also had evidence of a simultaneous response to epitopes presented on HLA A2 and HLA DP4. Conclusion: NY-ESO-1 ISCOM® vaccine was safe, well tolerated and generated both humoral and cellular NY-ESO-1 specific responses. Future studies will focus on identifying responses to other epitopes as well as undertaking trials in patients with evaluable disease to immune and clinical responses. This abstract was published in Cancer Immunity, a Cancer Research Institute journal that ceased publication in 2013 and is now provided online in association with Cancer Immunology Research.