Anticancer activity of tuftsin-derived T peptide in postoperative residual tumors.
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.
aDepartment of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine bCenter for Clinical Laboratory, Airforce General Hospital of Chinese PLA, Beijing, People's Republic of China.
Yinghong
Y
An
Linna
L
Li
Dexuan
D
Yang
Na
N
Jia
Chengwang
C
Xu
Qiong
Q
Wang
Shanshan
S
Wang
Shoujun
S
Yuan
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018572:Disease-Free Survival; D006801:Humans; D008239:Lysine / Q000737:chemistry; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018365:Neoplasm, Residual / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D014405:Tuftsin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha; D008239:Lysine; D014405:Tuftsin