1. Immunomodulatory and enhanced antitumor activity of a modified thymosin α1 in melanoma and lung cancer
- Author
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Fanwen Wang, Bin Li, Heng Zheng, Xingzhen Lao, Qingqing Li, and Pengcheng Fu
- Subjects
0301 basic medicine ,Lung Neoplasms ,Thymalfasin ,Recombinant Fusion Proteins ,T-Lymphocytes ,medicine.medical_treatment ,Mice, Nude ,Pharmaceutical Science ,Antineoplastic Agents ,Lymphocyte Activation ,Protein Structure, Secondary ,Mice ,03 medical and health sciences ,Adjuvants, Immunologic ,In vivo ,Cell Line, Tumor ,Immune Tolerance ,medicine ,Animals ,Humans ,Tumor-homing Peptide iRGD ,Lung cancer ,Melanoma ,Cell Proliferation ,CD86 ,Mice, Inbred BALB C ,Mice, Inbred ICR ,Chemistry ,Circular Dichroism ,Cancer ,Immunosuppression ,Trifluoroethanol ,medicine.disease ,Xenograft Model Antitumor Assays ,Fusion protein ,Mice, Inbred C57BL ,Thymosin ,030104 developmental biology ,Cancer research ,Female ,B7-2 Antigen ,Oligopeptides - Abstract
Tumor-targeted therapy is an attractive strategy for cancer treatment. Peptide hormone thymosin α1 (Tα1) has been used against several diseases, including cancer, but its activity is pleiotropic. Herein, we designed a fusion protein Tα1-iRGD by introducing the tumor homing peptide iRGD to Tα1. Results show that Tα1-iRGD can promote T-cell activation and CD86 expression, thereby exerting better effect and stronger inhibitory against melanoma and lung cancer, respectively, than Tα1 in vivo. These effects are indicated by the reduced densities of tumor vessels and Tα1-iRGD accumulation in tumors. Moreover, compared with Tα1, Tα1-iRGD can attach more B16F10 and H460 cells and exhibits significantly better immunomodulatory activity in immunosuppression models induced by hydrocortisone. Circular dichroism spectroscopy and structural analysis results revealed that Tα1 and Tα1-iRGD both adopted a helical confirmation in the presence of trifluoroethanol, indicating the structural basis of their functions. These findings highlight the vital function of Tα1-iRGD in tumor-targeted therapy and suggest that Tα1-iRGD is a better antitumor drug than Tα1.
- Published
- 2018