Hrouda D, Souberbielle B E, Kayaga J, Corbishley C M, Kirby R S, Dalgleish A G
Department of Urology, St George's Hospital, London, UK.
Br J Urol. 1998 Dec;82(6):870-6. doi: 10.1046/j.1464-410x.1998.00881.x.
To evaluate the potential of heat-killed Mycobacterium vaccae (SRL172) as a nonspecific immunostimulant and as an adjuvant to whole tumour cell vaccination in the rat model of prostate cancer.
SRL172 was used as a vaccine in the prevention and treatment of subcutaneous tumours in rats. Prevention experiments were conducted using subcutaneous MAT-LyLu tumours in Copenhagen rats, comparing vaccination with SRL172 alone, SRL172 plus autologous cells, and bacille Calmette-Guèrin (BCG) plus autologous cells before tumour implantation. Treatment experiments were conducted using subcutaneous MAT-LyLu tumours in the Copenhagen rat and subcutaneous PAIII tumours in the Lobund-Wistar rat. Tumours were induced by subcutaneous injection with tumour cells. Animals were then vaccinated with autologous cells, autologous cells plus SRL172, or SRL172 alone.
SRL172 was effective as an adjuvant to autologous whole tumour cell vaccination in the prevention of MAT-LyLu tumours and the survival benefit was equivalent to that provided when the adjuvant was live-attenuated BCG. SRL172 alone did not reduce tumour take or tumour growth in this model and neither strategy was effective in delaying the growth of established MAT-LyLu tumours. In the Lobund-Wistar rat vaccination with autologous whole tumour cells and SRL172 significantly delayed the growth of established tumours.
Mycobacterium vaccae deserves further evaluation as an adjuvant to whole tumour cell vaccination in a phase I clinical trial in patients with prostate cancer.
在前列腺癌大鼠模型中评估热灭活的母牛分枝杆菌(SRL172)作为非特异性免疫刺激剂以及全肿瘤细胞疫苗佐剂的潜力。
SRL172用作大鼠皮下肿瘤预防和治疗的疫苗。预防实验采用哥本哈根大鼠皮下接种MAT-LyLu肿瘤,在肿瘤植入前比较单独接种SRL172、SRL172加自体细胞以及卡介苗(BCG)加自体细胞的免疫效果。治疗实验采用哥本哈根大鼠皮下接种MAT-LyLu肿瘤以及Lobund-Wistar大鼠皮下接种PAIII肿瘤。通过皮下注射肿瘤细胞诱导肿瘤形成。然后动物分别接种自体细胞、自体细胞加SRL172或单独接种SRL172。
SRL172作为自体全肿瘤细胞疫苗的佐剂在预防MAT-LyLu肿瘤方面有效,其生存获益与使用减毒活卡介苗作为佐剂时相当。在该模型中,单独使用SRL172既不能减少肿瘤接种率也不能抑制肿瘤生长,两种策略均不能有效延缓已形成的MAT-LyLu肿瘤的生长。在Lobund-Wistar大鼠中,接种自体全肿瘤细胞和SRL172可显著延缓已形成肿瘤的生长。
母牛分枝杆菌作为前列腺癌患者I期临床试验中全肿瘤细胞疫苗的佐剂值得进一步评估。