Axl and EGFR Dual-Specific Binding Affibody for Targeted Therapy in Nasopharyngeal Carcinoma
Nasopharyngeal carcinoma (NPC) is a tumor of the head and neck, with a higher incidence in southern China and Southeast Asia. Radiotherapy and chemotherapy are the main treatments; however, metastasis and recurrence remain the main causes of treatment failure. Further, the majority of patients are d...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-11-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/13/22/1823 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846154053651791872 |
|---|---|
| author | Saidu Kamara He Wen Yanru Guo Ying Liu Lei Liu Wangqi Du Jun Chen Shanli Zhu Lifang Zhang |
| author_facet | Saidu Kamara He Wen Yanru Guo Ying Liu Lei Liu Wangqi Du Jun Chen Shanli Zhu Lifang Zhang |
| author_sort | Saidu Kamara |
| collection | DOAJ |
| description | Nasopharyngeal carcinoma (NPC) is a tumor of the head and neck, with a higher incidence in southern China and Southeast Asia. Radiotherapy and chemotherapy are the main treatments; however, metastasis and recurrence remain the main causes of treatment failure. Further, the majority of patients are diagnosed in the late stage due to lack of tumor-specific biomarker for early diagnosis. Therefore, an effective treatment and early detection can improve the outcome of patient with NPC. Axl and EGFR are co-expressed in NPC tissues and play key roles in tumor proliferation, migration, and invasion, which are often correlated with poor prognosis and therapy resistance. In this study, we generated a novel bispecific affibody (Z<sub>239-1907</sub>) for the dual targeting and inhibition of Axl and EGFR expression in NPC-positive cells both in vitro and in vivo. The in vitro experiments demonstrated that Z<sub>239-1907</sub> had more pronounced antitumor effects than either modality alone (Z<sub>AXL</sub>239 or Z<sub>EGFR</sub>1907) in NPC-positive cells. Further, mice bearing NPC-positive tumors showed significant inhibition in tumor growth after treatment with Z<sub>239-1907</sub> compared to Z<sub>AXL</sub>239 and Z<sub>EGFR</sub>1907. The in vivo tumor targeting ability and imaging also showed that Z<sub>239-1907</sub> specifically and selectively targeted NPC xenograft mice models and accumulate at tumor site as early as 30 min and disappeared within 24 h post-injection. Collectively, these results suggest that Z<sub>239-1907</sub> dual-target affibody is a promising therapeutic agent and a molecular imaging probe for early diagnosis in NPC. |
| format | Article |
| id | doaj-art-d2299e7824204e85b4bd5d3083c5dfc1 |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj-art-d2299e7824204e85b4bd5d3083c5dfc12024-11-26T17:56:40ZengMDPI AGCells2073-44092024-11-011322182310.3390/cells13221823Axl and EGFR Dual-Specific Binding Affibody for Targeted Therapy in Nasopharyngeal CarcinomaSaidu Kamara0He Wen1Yanru Guo2Ying Liu3Lei Liu4Wangqi Du5Jun Chen6Shanli Zhu7Lifang Zhang8Institute of Molecular Virology and Immunology, Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, ChinaInstitute of Molecular Virology and Immunology, Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, ChinaInstitute of Molecular Virology and Immunology, Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, ChinaInstitute of Molecular Virology and Immunology, Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, ChinaInstitute of Molecular Virology and Immunology, Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, ChinaInstitute of Molecular Virology and Immunology, Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, ChinaInstitute of Molecular Virology and Immunology, Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, ChinaInstitute of Molecular Virology and Immunology, Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, ChinaInstitute of Molecular Virology and Immunology, Department of Microbiology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, ChinaNasopharyngeal carcinoma (NPC) is a tumor of the head and neck, with a higher incidence in southern China and Southeast Asia. Radiotherapy and chemotherapy are the main treatments; however, metastasis and recurrence remain the main causes of treatment failure. Further, the majority of patients are diagnosed in the late stage due to lack of tumor-specific biomarker for early diagnosis. Therefore, an effective treatment and early detection can improve the outcome of patient with NPC. Axl and EGFR are co-expressed in NPC tissues and play key roles in tumor proliferation, migration, and invasion, which are often correlated with poor prognosis and therapy resistance. In this study, we generated a novel bispecific affibody (Z<sub>239-1907</sub>) for the dual targeting and inhibition of Axl and EGFR expression in NPC-positive cells both in vitro and in vivo. The in vitro experiments demonstrated that Z<sub>239-1907</sub> had more pronounced antitumor effects than either modality alone (Z<sub>AXL</sub>239 or Z<sub>EGFR</sub>1907) in NPC-positive cells. Further, mice bearing NPC-positive tumors showed significant inhibition in tumor growth after treatment with Z<sub>239-1907</sub> compared to Z<sub>AXL</sub>239 and Z<sub>EGFR</sub>1907. The in vivo tumor targeting ability and imaging also showed that Z<sub>239-1907</sub> specifically and selectively targeted NPC xenograft mice models and accumulate at tumor site as early as 30 min and disappeared within 24 h post-injection. Collectively, these results suggest that Z<sub>239-1907</sub> dual-target affibody is a promising therapeutic agent and a molecular imaging probe for early diagnosis in NPC.https://www.mdpi.com/2073-4409/13/22/1823affibody moleculesnasopharyngeal carcinomaAxlEGFRtargeted therapy |
| spellingShingle | Saidu Kamara He Wen Yanru Guo Ying Liu Lei Liu Wangqi Du Jun Chen Shanli Zhu Lifang Zhang Axl and EGFR Dual-Specific Binding Affibody for Targeted Therapy in Nasopharyngeal Carcinoma Cells affibody molecules nasopharyngeal carcinoma Axl EGFR targeted therapy |
| title | Axl and EGFR Dual-Specific Binding Affibody for Targeted Therapy in Nasopharyngeal Carcinoma |
| title_full | Axl and EGFR Dual-Specific Binding Affibody for Targeted Therapy in Nasopharyngeal Carcinoma |
| title_fullStr | Axl and EGFR Dual-Specific Binding Affibody for Targeted Therapy in Nasopharyngeal Carcinoma |
| title_full_unstemmed | Axl and EGFR Dual-Specific Binding Affibody for Targeted Therapy in Nasopharyngeal Carcinoma |
| title_short | Axl and EGFR Dual-Specific Binding Affibody for Targeted Therapy in Nasopharyngeal Carcinoma |
| title_sort | axl and egfr dual specific binding affibody for targeted therapy in nasopharyngeal carcinoma |
| topic | affibody molecules nasopharyngeal carcinoma Axl EGFR targeted therapy |
| url | https://www.mdpi.com/2073-4409/13/22/1823 |
| work_keys_str_mv | AT saidukamara axlandegfrdualspecificbindingaffibodyfortargetedtherapyinnasopharyngealcarcinoma AT hewen axlandegfrdualspecificbindingaffibodyfortargetedtherapyinnasopharyngealcarcinoma AT yanruguo axlandegfrdualspecificbindingaffibodyfortargetedtherapyinnasopharyngealcarcinoma AT yingliu axlandegfrdualspecificbindingaffibodyfortargetedtherapyinnasopharyngealcarcinoma AT leiliu axlandegfrdualspecificbindingaffibodyfortargetedtherapyinnasopharyngealcarcinoma AT wangqidu axlandegfrdualspecificbindingaffibodyfortargetedtherapyinnasopharyngealcarcinoma AT junchen axlandegfrdualspecificbindingaffibodyfortargetedtherapyinnasopharyngealcarcinoma AT shanlizhu axlandegfrdualspecificbindingaffibodyfortargetedtherapyinnasopharyngealcarcinoma AT lifangzhang axlandegfrdualspecificbindingaffibodyfortargetedtherapyinnasopharyngealcarcinoma |