ABSTRACT

Background: 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)

Matherial and methods: 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.

Results: 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.

Conclusions: 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.

摘要

背景：蕈样肉芽肿（MF）是一种原发性皮肤受累的低级别 T 细胞淋巴瘤，占所有原发性皮肤淋巴瘤的一半以上。由于可用的治疗方法有限，MF 的治疗非常具有挑战性。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® (IR700) 结合的单克隆抗体和近红外光。在这项研究中，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 的影响

材料和方法： MF 衍生的 My-La CD4+ 细胞与与 IR700 偶联的抗 CLA 抗体一起孵育，然后用 690 nm 近红外光照射。照射后24小时通过碘化丙啶染色和流式细胞术评估细胞死亡。

结果：用抗 CLA 或光照射处理表现出非常温和的促死亡作用，而用与 IR700 偶联的抗 CLA 抗体处理，然后用 690 nm 近红外光照射诱导 MF 细胞的死亡显着增加线。

结论：NIR-PIT靶向CLA治疗MF显示出显着的抗肿瘤作用。因此，CLA 靶向 NIR-PIT 可能是治疗 MF 以及其他以 CLA+ 皮肤浸润 T 细胞为特征的皮肤疾病的有希望的治疗方法。