Autologous hybrid cell fusion vaccine in a spontaneous intermediate model of breast carcinoma
Autologous hybrid cell fusion vaccine in a spontaneous intermediate model of breast carcinoma
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DOI：
10.4142/jvs.2019.20.e48
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发表时间：
2019-09-01
影响因子：
1.8
通讯作者：
Smith, Bruce F.
中科院分区：
文献类型：
--
作者：
Bird, R. Curtis;DeInnocentes, Patricia;Smith, Bruce F.
乳腺癌是影响女性和生殖完整的雌性犬的最常见的恶性肿瘤之一，如果不进行有效治疗，会导致转移性疾病死亡。为了更好地控制疾病进展，将来自恶性犬乳腺癌的犬乳腺肿瘤（CMT）细胞与自体树突状细胞（DC）融合，以产生用于诊断为自发性乳腺癌的犬患者的活杂交细胞融合疫苗。从外周血中高速分选罕见的自体犬患者DC提供了融合疫苗的自体组分，并且以高速率产生了与主要组织相容性复合物不匹配的CMT细胞的融合。每例患者在手术切除后以3周的间隔接种3次疫苗，并联合免疫刺激性寡核苷酸和吉西他滨辅助治疗。免疫的患者动物比对照患者（中位存活期184天）存活长3.3倍（中位存活期（III天）），并且似乎还表现出提高的生活质量。对诊断为炎性乳腺癌的接种疫苗患者进行比较，发现中位生存期非常短（42天），表明疫苗接种没有影响。数据显示，在患者动物中开发旨在改善犬乳腺癌管理的自体活DC疫苗策略可以成功，并且可以鉴定可转化的抗原，以促进犬和人类患者的有效免疫。
Breast cancer is among the most common malignancies affecting women and reproductively intact female dogs, resulting in death from metastatic disease if not treated effectively. To better manage the disease progression, canine mammary tumor (CMT) cells derived from malignant canine mammary cancers were fused to autologous dendritic cells (DCs) to produce living hybrid-cell fusion vaccines for canine patients diagnosed with spontaneous mammary carcinoma. The high-speed sorting of rare autologous canine patient DCs from the peripheral blood provides the autologous component of fusion vaccines, and fusion to major histocompatibility complex-unmatched CMT cells were produced at high rates. The vaccinations were delivered to each patient following a surgical resection 3 times at 3-week intervals in combination with immuno-stimulatory oligonucleotides and Gemcitabine adjunct therapy. The immunized patient animals survived 3.3-times longer (median survival (iii days) than the control patients (median survival 184 days) and also appeared to exhibit an enhanced quality of life. A comparison of vaccinated patients diagnosed with inflammatory mammary carcinoma resulted in a very short median survival (42 days), suggesting no effect of vaccination. The data showed that the development of autologous living DC-based vaccine strategies in patient animals designed to improve the management of canine mammary carcinoma can be successful and may allow an identification of the antigens that can be translatable to promote effective immunity in canine and human patients.