Tsuchiya Tomoko, Shiraishi Kenshiro, Nakagawa Keiichi, Kim Jae-Ryong, Kanegasaki Shiro
Research Center for Medical Science, Yeungnam University, Republic of Korea.
Central Lab, Effector Cell Institute Inc., Japan.
Clin Transl Radiat Oncol. 2018 Feb 23;10:7-12. doi: 10.1016/j.ctro.2018.02.004. eCollection 2018 Mar.
Intravenous administration of a single amino acid-substituted chemokine CCL3 derivative named eMIP elicits the abscopal effect (an effect distal to the target), after local irradiation at a tumor-bearing site. To distinguish the active portion of eMIP, we tested the antitumor activity of chemically synthesized partial peptides of eMIP. Synthetic peptide has various advantages in its clinical application.
Colon26 adenocarcinoma cells were implanted subcutaneously in the right and left flanks of mice. eMIP, CCL3 or any of synthesized peptides was administered intravenously, either after irradiating the right flank. The effect was evaluated by tumor-growth inhibition.
Q/C peptide, a synthetic peptide of amino acids 22-51 of eMIP has no chemotaxis-inducing ability but yet enhanced tumor growth inhibition at the non-irradiated sites, recapitulating the effect of eMIP with local irradiation. Co-administration of this peptide and HSP70 also inhibited tumor growth.
Q/C peptide maps to the eMIP β-sheet: 3 adjacent anti-parallel strands connected by the β-hairpins, is the active portion of eMIP necessary for an immunomodulatory antitumor effect. This experimental reduction furthers our understanding of the underlying mechanism of the abscopal effect. The data will open the way for therapeutic application of like peptides.
在荷瘤部位进行局部照射后，静脉注射一种名为eMIP的单氨基酸取代趋化因子CCL3衍生物可引发远隔效应（靶区以外的效应）。为了区分eMIP的活性部分，我们测试了化学合成的eMIP部分肽段的抗肿瘤活性。合成肽在临床应用中有多种优势。
将结肠26腺癌细胞皮下植入小鼠的左右侧腹。在照射右侧腹后，静脉注射eMIP、CCL3或任何一种合成肽。通过肿瘤生长抑制来评估效果。
Q/C肽是eMIP第22 - 51位氨基酸的合成肽，没有趋化诱导能力，但却增强了未照射部位的肿瘤生长抑制，重现了局部照射时eMIP的效果。该肽与热休克蛋白70共同给药也能抑制肿瘤生长。
Q/C肽定位到eMIP的β折叠结构：由β发夹连接的3条相邻反平行链，是eMIP产生免疫调节抗肿瘤效应所必需的活性部分。这一实验结果进一步加深了我们对远隔效应潜在机制的理解。这些数据将为类似肽的治疗应用开辟道路。
