ABSTRACT
ATP binding cassette subfamily B member 5 (ABCB5) has been identified as a tumour-initiating cell marker and is expressed in various malignancies, including melanoma. Moreover, treatment with anti-ABCB5 monoclonal antibodies has been shown to inhibit tumour growth in xenotransplantation models. Therefore, ABCB5 represents a potential target for cancer immunotherapy. However, cellular immune responses against ABCB5 in humans have not been described so far. Here, we investigated whether ABCB5-reactive T cells are present in human melanoma patients and tested the applicability of ABCB5-derived peptides for experimental induction of human T cell responses. Peripheral blood mononuclear cells (PBMNC) isolated from blood samples of melanoma patients (n = 40) were stimulated with ABCB5 peptides, followed by intracellular cytokine staining (ICS) for interferon (IFN)-γ and tumour necrosis factor (TNF)-α. To evaluate immunogenicity of ABCB5 peptides in naive healthy donors, CD8 T cells were co-cultured with ABCB5 antigen-loaded autologous dendritic cells (DC). ABCB5 reactivity in expanded T cells was assessed similarly by ICS. ABCB5-reactive CD8+ T cells were detected ex vivo in 19 of 29 patients, melanoma antigen recognised by T cells (MART-1)-reactive CD8+ T cells in six of 21 patients. In this small, heterogeneous cohort, reactivity against ABCB5 was significantly higher than against MART-1. It occurred significantly more often and independently of clinical characteristics. Reactivity against ABCB5 could be induced in 14 of 16 healthy donors in vitro by repeated stimulation with peptide-loaded autologous DC. As ABCB5-reactive CD8 T cells can be found in the peripheral blood of melanoma patients and an ABCB5-specific response can be induced in vitro in naive donors, ABCB5 could be a new target for immunotherapies in melanoma.
Subject(s)
ATP Binding Cassette Transporter, Subfamily B, Member 1/immunology , Antigens, Neoplasm/immunology , CD8-Positive T-Lymphocytes/immunology , Melanoma/immunology , ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily B, Member 1/chemistry , Amino Acid Sequence , CD8-Positive T-Lymphocytes/metabolism , Cytokines/metabolism , Cytotoxicity, Immunologic , Dendritic Cells/immunology , Dendritic Cells/metabolism , Epitopes, T-Lymphocyte/chemistry , Epitopes, T-Lymphocyte/immunology , Female , Humans , Immunotherapy , Lymphocyte Activation , Male , Melanoma/diagnosis , Melanoma/metabolism , Melanoma/therapy , Neoplasm Staging , Peptides/chemistry , Peptides/immunologyABSTRACT
The treatment of acute schizophrenic disorders with large doses of droperidol was compared to clozapine and clopenthixol in a special study. Apart from the clinical protocol, psychometric test for the assessment of social behaviour and thought disorders were used. The advantages of the treatment with droperidol, especially in highly disturbed acute schizophrenic patients, are shown and discussed by means of the results of psychological tests and clinical experience.
