Hrouda D, Todryk S M, Perry M J, Souberbielle B E, Kayaga J, Kirby R S, Dalgleish A G
Division of Oncology and Department of Urology, St George's Hospital, London Department of Molecular Medicine, Kings College Hospital, London, UK.
BJU Int. 2000 Oct;86(6):742-8. doi: 10.1046/j.1464-410x.2000.00887.x.
To investigate cancer immunotherapy using whole allogeneic (differing tissue-type) tumour cells as vaccines in the rat prostate cancer model. Materials and methods Two rat models of prostate cancer were used; MAT-LyLu tumours which grow in Copenhagen rats and PAIII tumours which grow in Lobund-Wistar rats, with crossover of the cell lines to test allogeneic vaccination. The cell lines were immunologically characterized by flow cytometry. Irradiated tumour cells were administered as subcutaneous vaccines either before tumour challenge or after tumour establishment (both subcutaneous). A preparation of heat-killed Mycobacterium vaccae bacilli (SRL172) was used as an adjuvant to increase vaccine efficiency.
Flow cytometry analysis of the cell lines showed that the PAIII cells had higher levels of major histocompatibility complex (MHC) class I and intercellular adhesion molecule (ICAM-1) expression than the MAT-LyLu cells. However, both tumour cell lines were rejected in their allogeneic hosts. Prophylactic vaccination with allogeneic MAT-LyLu cells protected against PAIII tumour challenge in Lobund-Wistar rats, with 80% of animals surviving for > 5 months, compared with 40% for animals receiving autologous cells. The immunity was prolonged, as rats were protected when rechallenged 5 months later. In Copenhagen rats allogeneic PAIII cells protected against the more aggressive MAT-LyLu tumour challenge only when the cells were combined with SRL172. Initial therapy experiments showed that vaccination with the cell lines mediated only limited tumour regression in the Lobund-Wistar rats.
The allogeneic tumour cell vaccination model described is valuable for assessing the principle and efficacy of allogeneic prostate cancer cell vaccines for clinical use.
在大鼠前列腺癌模型中研究使用全同种异体（不同组织类型）肿瘤细胞作为疫苗进行癌症免疫治疗。材料与方法 使用了两种大鼠前列腺癌模型；在哥本哈根大鼠中生长的MAT-LyLu肿瘤和在洛邦德-威斯塔大鼠中生长的PAIII肿瘤，将细胞系交叉使用以测试同种异体疫苗接种。通过流式细胞术对细胞系进行免疫表征。在肿瘤攻击前或肿瘤形成后（均为皮下注射）将经辐照的肿瘤细胞作为皮下疫苗给药。使用热灭活的母牛分枝杆菌（SRL172）制剂作为佐剂以提高疫苗效率。
细胞系的流式细胞术分析表明，PAIII细胞的主要组织相容性复合体（MHC）I类和细胞间黏附分子（ICAM-1）表达水平高于MAT-LyLu细胞。然而，两种肿瘤细胞系在其同种异体宿主中均被排斥。用同种异体MAT-LyLu细胞进行预防性疫苗接种可保护洛邦德-威斯塔大鼠免受PAIII肿瘤攻击，80%的动物存活超过5个月，而接受自体细胞的动物存活率为40%。免疫反应得以延长，因为大鼠在5个月后再次受到攻击时受到了保护。在哥本哈根大鼠中，只有当同种异体PAIII细胞与SRL172联合使用时，才能保护其免受更具侵袭性的MAT-LyLu肿瘤攻击。初步治疗实验表明，用细胞系进行疫苗接种在洛邦德-威斯塔大鼠中仅介导了有限的肿瘤消退。
所描述的同种异体肿瘤细胞疫苗接种模型对于评估用于临床的同种异体前列腺癌细胞疫苗的原理和疗效具有重要价值。
