Allogeneic whole-tumour cell vaccination in the rat model of prostate cancer

被引:30
作者
Hrouda, D
Todryk, SM
Perry, MJA
Souberbielle, BE
Kayaga, J
Kirby, RS
Dalgleish, AG
机构
[1] Univ London St Georges Hosp, Sch Med, Div Oncol, London SW17 0RE, England
[2] Univ London St Georges Hosp, Dept Urol, London SW17 0RE, England
[3] Kings Coll Hosp London, Dept Mol Med, London, England
[4] Royal Marsden Hosp, Lung Unit, Surrey, England
关键词
allogeneic vaccine; prostate cancer; immunotherapy; rat model;
D O I
10.1046/j.1464-410x.2000.00887.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Objective 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. Results 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. Conclusion The allogeneic tumour cell vaccination model described is valuable for assessing the principle and efficacy of allogeneic prostate cancer cell vaccines for clinical use.
引用
收藏
页码:742 / 748
页数:7
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