Burkholz Scott R, Herst Charles V, Carback Richard T, Harris Paul E, Rubsamen Reid M
Flow Pharma Inc., Warrensville Heights, OH 44128, USA.
Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
Vaccines (Basel). 2023 Mar 13;11(3):644. doi: 10.3390/vaccines11030644.
A triple negative breast cancer model using the murine 4T1 tumor cell line was used to explore the efficacy of an adjuvanted survivin peptide microparticle vaccine using tumor growth as the outcome metric. We first performed tumor cell dose titration studies to determine a tumor cell dose that resulted in sufficient tumor takes but allowed multiple serial measurements of tumor volumes, yet with minimal morbidity/mortality within the study period. Later, in a second cohort of mice, the survivin peptide microparticle vaccine was administered via intraperitoneal injection at the study start with a second dose given 14 days later. An orthotopic injection of 4T1 cells into the mammary tissue was performed on the same day as the administration of the second vaccine dose. The mice were followed for up to 41 days with subcutaneous measurements of tumor volume made every 3-4 days. Vaccination with survivin peptides was associated with a peptide antigen-specific gamma interferon enzyme-linked immunosorbent spot response in the murine splenocyte population but was absent from the control microparticle group. At the end of the study, we found that vaccination with adjuvanted survivin peptide microparticles resulted in statistically significant slower primary tumor growth rates in BALB/c mice challenged with 4T1 cells relative to the control peptideless vaccination group. These studies suggest that T cell immunotherapy specifically targeting survivin might be an applicable neoadjuvant immunotherapy therapy for triple negative breast cancer. More preclinical studies and clinical trials are needed to explore this concept further.
使用鼠源4T1肿瘤细胞系的三阴性乳腺癌模型,以肿瘤生长作为结果指标,来探索佐剂化生存素肽微粒疫苗的疗效。我们首先进行了肿瘤细胞剂量滴定研究,以确定能产生足够肿瘤接种成功率、允许多次连续测量肿瘤体积且在研究期间发病率/死亡率最低的肿瘤细胞剂量。随后,在第二批小鼠中,在研究开始时通过腹腔注射给予生存素肽微粒疫苗,并在14天后给予第二剂。在给予第二剂疫苗的同一天,将4T1细胞原位注射到乳腺组织中。对小鼠进行长达41天的跟踪,每3 - 4天皮下测量一次肿瘤体积。用生存素肽进行疫苗接种与鼠脾细胞群体中肽抗原特异性γ干扰素酶联免疫斑点反应相关,但在对照微粒组中未出现。在研究结束时,我们发现,与无肽对照疫苗接种组相比,用佐剂化生存素肽微粒进行疫苗接种使接受4T1细胞攻击的BALB/c小鼠的原发性肿瘤生长速度在统计学上显著减慢。这些研究表明,特异性靶向生存素的T细胞免疫疗法可能是一种适用于三阴性乳腺癌的新辅助免疫疗法。需要更多的临床前研究和临床试验来进一步探索这一概念。
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