Komatsu Noriko, Kosai Azuma, Kuroda Mikako, Hamakubo Takao, Abe Takahiro
Department of Oral and Maxillofacial Surgery of Dentistry, Kanagawa Dental University, Yokosuka 238-8570, Japan.
PhotoQ3 Inc., Tokyo 102-0084, Japan.
Biomedicines. 2024 Apr 29;12(5):973. doi: 10.3390/biomedicines12050973.
Photodynamic therapy (PDT) is a cancer-targeted treatment that uses a photosensitizer (PS) and irradiation of a specific wavelength to exert cytotoxic effects. To enhance the antitumor effect against head and neck squamous cell carcinoma (HNSCC), we developed a new phototherapy, intelligent targeted antibody phototherapy (iTAP). This treatment uses a combination of immunotoxin (IT) and a PS for PDT and light irradiation. In our prior study, we demonstrated that an immunotoxin (IT) consisting of an anti-ROBO1 antibody conjugated to saporin, when used in combination with the photosensitizer (PS) disulfonated aluminum phthalocyanine (AlPcS2a) and irradiated with light at the appropriate wavelength, resulted in increased cytotoxicity against head and neck squamous cell carcinoma (HNSCC) cells. ROBO1 is a receptor known to be involved in the progression of cancer. In this study, we newly investigate the iTAP targeting epidermal growth factor receptor (EGFR) which is widely used as a therapeutic target for HNSCC.
We checked the expression of EGFR in HNSCC cell lines, SAS, HO-1-u-1, Sa3, and HSQ-89. We analyzed the cytotoxicity of saporin-conjugated anti-EGFR antibody (cetuximab) (IT-Cmab), mono-L-aspartyl chlorin e6 (NPe6, talaporfin sodium), and light (664 nm) irradiation (i.e., iTAP) in SAS, HO-1-u-1, Sa3, and HSQ-89 cells.
EGFR was expressed highly in Sa3, moderately in HO-1-u-1, SAS, and nearly not in HSQ-89. Cmab alone or IT-Cmab alone did not show cytotoxic effects in Sa3, HO-1-u-1, and HSQ-89 cells, which have moderate or low expression levels of EGFR protein. However, the iTAP method enhanced the cytotoxicity of IT-Cmab by the photodynamic effect in Sa3 and HO-1-u-1 cells, which have moderate levels of EGFR expression.
Our study is the first to report on the iTAP method using IT-Cmab and NPe6 for HNSCC. The cytotoxic effects are enhanced in cell lines with moderate levels of EGFR protein expression, but not in nonexpressing cell lines, which is expected to expand the range of therapeutic windows and potentially reduce complications.
光动力疗法（PDT）是一种癌症靶向治疗方法，它使用光敏剂（PS）和特定波长的照射来发挥细胞毒性作用。为了增强对头颈部鳞状细胞癌（HNSCC）的抗肿瘤作用，我们开发了一种新的光疗方法，即智能靶向抗体光疗（iTAP）。这种治疗方法将免疫毒素（IT）和PS结合用于PDT及光照射。在我们之前的研究中，我们证明了一种由与皂草素偶联的抗ROBO1抗体组成的免疫毒素（IT），当与光敏剂（PS）二磺酸铝酞菁（AlPcS2a）联合使用并在适当波长下照射时，对头颈部鳞状细胞癌（HNSCC）细胞的细胞毒性增加。ROBO1是一种已知参与癌症进展的受体。在本研究中，我们新研究了靶向表皮生长因子受体（EGFR）的iTAP，EGFR被广泛用作HNSCC的治疗靶点。
我们检测了HNSCC细胞系SAS、HO-1-u-1、Sa3和HSQ-89中EGFR的表达。我们分析了与皂草素偶联的抗EGFR抗体（西妥昔单抗）（IT-Cmab）、单-L-天冬氨酸氯in e6（NPe6，他拉泊芬钠）和光（664nm）照射（即iTAP）对SAS、HO-1-u-1、Sa3和HSQ-89细胞的细胞毒性。
EGFR在Sa3中高表达，在HO-1-u-1、SAS中中度表达，在HSQ-89中几乎不表达。单独的Cmab或单独的IT-Cmab在EGFR蛋白表达水平中等或较低的Sa3、HO-1-u-1和HSQ-89细胞中未显示细胞毒性作用。然而，iTAP方法通过光动力效应增强了IT-Cmab在EGFR表达水平中等的Sa3和HO-1-u-1细胞中的细胞毒性。
我们的研究首次报道了使用IT-Cmab和NPe6治疗HNSCC的iTAP方法。在EGFR蛋白表达水平中等的细胞系中细胞毒性增强，但在无表达的细胞系中未增强，这有望扩大治疗窗口范围并潜在减少并发症。
