Immunomodulatory and enhanced antitumor activity of a modified thymosin α1 in melanoma and lung cancer.
Wang. Fanwen F; Li. Bin B; Fu. Pengcheng P; Li. Qingqing Q; Zheng. Heng H; Lao. Xingzhen X
Key Findings
- Tα1‑iRGD boosts T‑cell activation and CD86 expression more than plain Tα1
- The fusion protein accumulates in tumors and reduces tumor blood vessel density
- In mouse models of melanoma and lung cancer, Tα1‑iRGD shows stronger anti‑tumor effects than Tα1
Practical Outcomes
- At this stage the findings are interesting but not ready for self‑experimentation. They suggest that future cancer‑focused formulations of thymosin‑alpha‑1 might be more effective, but no actionable dosing or safety data for humans are available yet.
Summary
Scientists attached a tumor‑seeking peptide (iRGD) to the immune‑boosting protein thymosin‑alpha‑1 and tested it in mice with melanoma and lung cancer. The new combo, called Tα1‑iRGD, activated immune cells better, gathered more in tumors, and slowed tumor growth more than regular thymosin‑alpha‑1. However, this work is still in early animal studies, so it doesn’t give a usable dosage or safety guide for people yet.
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.
Study Information
pubmed
2018
2018-06-19T00:00:00.000Z
10.1016/j.ijpharm.2018.06.041
17
58