Silic-Benussi Micol, Saponeri Andrea, Michelotto Anna, Russo Irene, Colombo Anna, Pelizzo Maria Guglielmina, Ciminale Vincenzo, Alaibac Mauro
Immunology and Molecular Oncology Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy.
Unit of Dermatology, University of Padua, Padova, Italy.
Expert Opin Biol Ther. 2021 Jul;21(7):977-981. doi: 10.1080/14712598.2021.1858791. Epub 2020 Dec 23.
: Mycosis fungoides (MF) is a low-grade T-cell lymphoma with primary cutaneous involvement accounting for more than half of all primary cutaneous lymphomas. The treatment of MF is very challenging due to the limited therapies available. Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed and highly selective cancer treatment that employs a monoclonal antibody conjugated to a photo-absorber dye, the hydrophilic phthalocyanine IRdye 700DX® (IR700), and near infrared light. In this study, we investigated the effect of NIR-PIT on MF targeting the cell-surface antigen cutaneous lymphocyte antigen (CLA): MF derived My-La CD4+ cells were incubated with the anti-CLA antibody conjugated to IR700 and then irradiated with a 690 nm near-infrared light. Cell death was evaluated by propidium iodide staining and flow cytometry 24 hours after irradiation.: Treatment with anti-CLA or light irradiation exhibited very modest pro-death effects, whereas treatment with the anti-CLA antibody conjugated to IR700 and then irradiation with a 690 nm near-infrared light induced a substantial increase in death in the MF cell line.: NIR-PIT targeting CLA to treat MF showed marked antitumour effects. As such, CLA-targeted NIR-PIT could be a promising treatment for MF and, possibly, other cutaneous diseases characterized by CLA+ skin infiltrating T-cells.
蕈样肉芽肿(MF)是一种低度T细胞淋巴瘤,主要累及皮肤,占所有原发性皮肤淋巴瘤的一半以上。由于可用治疗方法有限,MF的治疗极具挑战性。近红外光免疫疗法(NIR-PIT)是一种新开发的高选择性癌症治疗方法,它使用与光吸收染料(亲水性酞菁IRdye 700DX®,即IR700)偶联的单克隆抗体和近红外光。在本研究中,我们研究了NIR-PIT对靶向细胞表面抗原皮肤淋巴细胞抗原(CLA)的MF的作用:将MF来源的My-La CD4+细胞与与IR700偶联的抗CLA抗体孵育,然后用690nm近红外光照射。照射24小时后,通过碘化丙啶染色和流式细胞术评估细胞死亡情况。用抗CLA或光照射治疗显示出非常适度的促死亡作用,而用与IR700偶联的抗CLA抗体治疗,然后用690nm近红外光照射,可使MF细胞系的死亡率大幅增加。靶向CLA的NIR-PIT治疗MF显示出显著的抗肿瘤作用。因此,靶向CLA的NIR-PIT可能是MF以及其他以CLA+皮肤浸润T细胞为特征的皮肤疾病的一种有前景的治疗方法。