King Robert S, Tuthill Cynthia
SciClone Pharmaceuticals, Inc. , 950 Tower Lane, Suite 900, Foster City, CA, 94404 , USA +1 650 358 3459 ; +1 650 350 4862 ;
Expert Opin Biol Ther. 2015;15 Suppl 1:S41-9. doi: 10.1517/14712598.2015.1008446. Epub 2015 Feb 2.
Recent understanding of the complex pathophysiology of melanoma and severe sepsis suggests that immune-modulating compounds such as thymosin alpha 1 (INN: thymalfasin; abbreviated Ta1) could be useful in the treatment of these two unrelated immune-suppressing indications.
Three nonclinical murine models were utilized, including: i) a lung metastasis B16 model; ii) a B16-based tumor growth model; and iii) a cecal-ligation and puncture (CLP) sepsis model.
In the lung metastasis model, Ta1 treatment alone led to a 32% decrease in metastases (p < 0.05). Additionally, combinations of Ta1 and an anti-PD-1 antibody led to significantly fewer metastases than vehicle. In the tumor growth model, significant decreases in tumor growth were seen: 34% (p = 0.015) to 46% (p = 0.001) depending on the Ta1 dose. In the CLP sepsis model, Ta1 treatment showed a positive trend towards increased survival and decreased bacterial load. In this CLP model, Ta1 also appeared to have an effect on the levels of some biomarkers.
All three models demonstrated a benefit after treatment with Ta1, with no evidence of toxicity. These initial pilot studies support the hypothesis that immune-suppressive indications, including sepsis and melanoma, may be treated with Ta1 alone or by Ta1 in combination with other immunotherapies.
近期对黑色素瘤和严重脓毒症复杂病理生理学的认识表明，诸如胸腺肽α1（国际非专利药品名称：胸腺法新；缩写为Ta1）等免疫调节化合物可能有助于治疗这两种不相关的免疫抑制病症。
使用了三种非临床小鼠模型，包括：i）肺转移B16模型；ii）基于B16的肿瘤生长模型；iii）盲肠结扎和穿刺（CLP）脓毒症模型。
在肺转移模型中，单独使用Ta1治疗导致转移灶减少32%（p<0.05）。此外，Ta1与抗PD-1抗体联合使用导致的转移灶明显少于赋形剂组。在肿瘤生长模型中，观察到肿瘤生长显著降低：根据Ta1剂量不同，降低幅度为34%（p=0.015）至46%（p=0.001）。在CLP脓毒症模型中，Ta1治疗显示出存活增加和细菌载量降低的积极趋势。在该CLP模型中，Ta1似乎还对某些生物标志物的水平有影响。
所有三种模型在使用Ta1治疗后均显示出益处，且无毒性证据。这些初步的先导研究支持了这样的假设，即包括脓毒症和黑色素瘤在内的免疫抑制病症可能单独用Ta1治疗，或用Ta1与其他免疫疗法联合治疗。
