Immunomodulatory and enhanced antitumor activity of a modified thymosin α1 in melanoma and lung cancer

Tumor-targeted therapy is an attractive strategy for cancer treatment. Peptide hormone thymosin alpha 1 (T alpha 1) has been used against several diseases, including cancer, but its activity is pleiotropic. Herein, we designed a fusion protein T alpha 1-iRGD by introducing the tumor homing peptide iRGD to T alpha 1. Results show that T alpha 1-iRGD can promote T-cell activation and CD86 expression, thereby exerting better effect and stronger inhibitory against melanoma and lung cancer, respectively, than T alpha 1 in vivo. These effects are indicated by the reduced densities of tumor vessels and T alpha 1-iRGD accumulation in tumors. Moreover, compared with T alpha 1, T alpha 1-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 T alpha 1 and T alpha 1-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 T alpha 1-iRGD in tumor-targeted therapy and suggest that T alpha 1-iRGD is a better antitumor drug than T alpha 1.