Detection of ABCB5 tumour antigen ‐specific CD8+ T cells in melanoma patients and implications for immunotherapy

Summary 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 ...
Source: Clinical and Experimental Immunology - Category: Allergy & Immunology Authors: Tags: Original Article Source Type: research