Anticancer activity of tuftsin-derived T peptide in postoperative residual tumors

Abstract

Immune adjuvants have been used in cancer biotherapies to stimulate immune response to tumor cells. Despite their potential as anticancer reagents, there are several impediments to their use in clinical applications. In this study, we aim to modify the existing tuftsin structure and evaluate its antitumor activity in preclinical models. We synthesized a novel tuftsin derivative, namely, the T peptide (TP), by linking four tuftsin peptides, which showed enhanced stability in vivo. We then evaluated its anticancer activity in a postoperative residual tumor model in mice, where we surgically removed most of the primary tumor from the host, a procedure mimicking clinically postoperative patients. Despite the limited effect in intact solid tumors, TP strongly inhibited relapsed growth of residual tumors in postsurgical mice. Surgical resection of tumors accelerated residual tumor growth, but TP slowed down this process significantly. Interestingly, TP showed similar effects in human xenograft residual models. As an immunomodulator, TP could synergize the functions of macrophages, thus inhibiting the growth of cocultured tumor cells in vitro. Furthermore, TP could shift the macrophages to the tumor-suppressive M1 type and mobilize them to produce elevated cytotoxic TNF-α and NO. As a result, TP effectively prolonged the survival time of tumor-resected mice. Using the postoperative residual tumor models, we provide a body of evidence showing the antitumor activity of TP, which causes no obvious toxicity. Our study highlights the potential of TP as a postoperative adjuvant in cancer therapies.

Antitumor Effects of Orally and Intraperitoneally Administered Chitosan Oligosaccharides (COSs) on S180‐Bearing/Residual Mouse

“…In the second set of surgical trials after the transplantation of live tumor cells and the appearance of solid tumor formations as mentioned in Animal Tumor Model , a surgical extirpation of the tumor formation was carried out (Toshkova and others ) when the average tumor volume reached about 300 to 350 mm 3 . The volume of remaining tumor was approximately 40 to 100 mm 3 after anesthetization by intravenous injection with 0.5% sodium pentobarbital solution (An and others ). The animal model described above simulated that incomplete resection resulted in residual existing in the tumor focus after surgical removal of tumor tissue.…”

PEP06 polypeptide 30 exerts antitumour effect in colorectal carcinoma via inhibiting epithelial–mesenchymal transition

“…The animals were housed in a controlled environment at 23 ± 2°C under a 12 h dark/light cycle with free access to irradiated food and sterile water. We established a murine model with a postsurgical residual tumour to mimic the recurrence of solid tumour as described previously (An et al, 2014). The LOVO tumour cells (over 5 × 10 7 mL À1 ) were harvested and washed with sodium chloride.…”

Tuftsin-derived T-peptide prevents cellular immunosuppression and improves survival rate in septic mice

“…The elementary structure of tuftsin-derived T-peptide is (Thr-Lys-Pro-Arg-AAN)4-(Lys-AAN)2-Lys-AAN, which has been granted a patent in China (CN-101007842A). Recently, it had been demonstrated that tuftsin-derived T-peptide was a potential postoperative adjuvant in cancer therapy, and it showed an inhibitory effect on growth of residual tumor cells after surgical resection 42 . In the current study, the objective was to investigate the effect of tuftsin-derived T-peptide on cell-mediated immunity after LPS stimulation and the survival rate in septic mice.…”