The ZMAGE-A3 affitoxin 172-cpp has great potential for targeting therapy of tumors
4 affiliations
- 1Department of Urology II, Handan First Hospital
- 2Department of Microbiology and Immunology, Institute of Molecular Virology and Immunology, School of Basic Medical Sciences, Wenzhou Medical University
- 3Department of Vascular Surgery, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University
- 4Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University
Abstract
Background: The MAGE-A3 oncological antigen, a member of the cancer-testis protein family, is markedly overexpressed across various types of malignant tumors. Affibody molecules, a novel class of compact targeting proteins (~6.5 kDa), have been established as potent agents for molecular imaging and targeted cancer therapy. This study evaluates the designed an affibody molecules as novel agents by fusing a MAGE-A3 affibody molecule with modified Pseudomonas exotoxin (PE38KDEL) and a cell-penetrating peptide (cpp) to develop an affitoxin, ZMAGE-A3 affitoxin 172-cpp, and evaluated its anti-tumor efficacy.
Methods: we verified the expression of ZMAGE-A3 affitoxin 172-cpp by SDS-PAGE. MAGE-A3-positive cells was selected by qPCR. The internalization of ZMAGE-A3 affitoxin 172-cpp was detected using fluorescence imaging. Cell viability was detected using cell counting kit 8 (CCK-8) and colony formation assay. Cell apoptosis was measured by flow cytometry. The in vivo targeting ability of ZMAGE-A3 affitoxin 172-cpp was analyzed by near-infrared (NIR) imaging.
Results: ZMAGE-A3 affitoxin 172-cpp demonstrated precise binding to the MAGE-A3 protein in living cells. Moreover, the accumulation of DyLight755-labeled ZMAGE-A3 affitoxin 172-cpp in MAGE-A3-positive tumors was observed as early as 1 hour post-injection, with clearance by 48 hours. ZMAGE-A3 affitoxin 172-cpp effectively suppressed the viability and induced apoptosis of A375 and A2058 cells. The results from xenograft model indicated that ZMAGE-A3 affitoxin 172-cpp effectively repressed in vivo tumor growth.
Conclusion: Our findings support the potential of the ZMAGE-A3 affitoxin 172-cpp as a molecular imaging and therapeutic agent for MAGE-A3 positive cancer.
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BibTeX
@article{li2026zmagea3,
title = {{The ZMAGE-A3 affitoxin 172-cpp has great potential for targeting therapy of tumors}},
author = {Hongjing Li and Kui Chen and Li Shi and Yan-Ru Guo and Dong-Yin Xu and Xiang-Tao Zheng and Li-Fang Zhang},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1862676},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1862676/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The ZMAGE-A3 affitoxin 172-cpp has great potential for targeting therapy of tumors
AU - Hongjing Li
AU - Kui Chen
AU - Li Shi
AU - Yan-Ru Guo
AU - Dong-Yin Xu
AU - Xiang-Tao Zheng
AU - Li-Fang Zhang
PY - 2026
DA - 2026/10/28
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1862676
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1862676/full
AB - Background: The MAGE-A3 oncological antigen, a member of the cancer-testis protein family, is markedly overexpressed across various types of malignant tumors. Affibody molecules, a novel class of compact targeting proteins (~6.5 kDa), have been established as potent agents for molecular imaging and targeted cancer therapy. This study evaluates the designed an affibody molecules as novel agents by fusing a MAGE-A3 affibody molecule with modified Pseudomonas exotoxin (PE38KDEL) and a cell-penetrating peptide (cpp) to develop an affitoxin, ZMAGE-A3 affitoxin 172-cpp, and evaluated its anti-tumor efficacy. Methods: we verified the expression of ZMAGE-A3 affitoxin 172-cpp by SDS-PAGE. MAGE-A3-positive cells was selected by qPCR. The internalization of ZMAGE-A3 affitoxin 172-cpp was detected using fluorescence imaging. Cell viability was detected using cell counting kit 8 (CCK-8) and colony formation assay. Cell apoptosis was measured by flow cytometry. The in vivo targeting ability of ZMAGE-A3 affitoxin 172-cpp was analyzed by near-infrared (NIR) imaging. Results: ZMAGE-A3 affitoxin 172-cpp demonstrated precise binding to the MAGE-A3 protein in living cells. Moreover, the accumulation of DyLight755-labeled ZMAGE-A3 affitoxin 172-cpp in MAGE-A3-positive tumors was observed as early as 1 hour post-injection, with clearance by 48 hours. ZMAGE-A3 affitoxin 172-cpp effectively suppressed the viability and induced apoptosis of A375 and A2058 cells. The results from xenograft model indicated that ZMAGE-A3 affitoxin 172-cpp effectively repressed in vivo tumor growth. Conclusion: Our findings support the potential of the ZMAGE-A3 affitoxin 172-cpp as a molecular imaging and therapeutic agent for MAGE-A3 positive cancer.
SN - 2234-943X
ER -