Souberbielle B E, Knight B C, Morrow W J, Darling D, Fraziano M, Marriott J B, Cookson S, Farzaneh F, Dalgleish A G
Divisions of Oncology, St George's Hospital Medical School, London, UK.
Gene Ther. 1996 Oct;3(10):853-8.
The use of whole cell tumour vaccines in the treatment of malignant melanoma has given mixed results. Cytokine-transfected tumour cells as vaccine have shown efficacy in animal models but need to be compared with other means of enhancing a systemic anti-tumour immune response. A new generation of immunological adjuvants claimed to be more effective than the conventional adjuvants is now available for assessment. We have investigated the action of an oil-microemulsion adjuvant formulation (IDEC antigen formulation (IDEC-AF)) in the B16-F10 murine melanoma model. After standardisation of the whole cell tumour vaccination protocol we showed that mice vaccinated with whole irradiated cells combined with IDEC-AF produced a significant inhibition of tumour growth, following a challenge with live tumour cells, when compared with mice vaccinated with whole cell vaccine alone. IDEC-AF was superior to two conventional adjuvants, namely alum and incomplete Freund's adjuvant and a more reliable response was achieved with the oil-microemulsion adjuvant compared with IL-2-transfected cells. In addition, the adjuvant was comparable in efficacy to IL-4-transfected B16-F10 cells. Given the practical difficulty in using cytokine-transfected tumour cells and the limited therapeutic range of some cytokines, a cheap and easy to deliver adjuvant formulation proved equally or more effective than some of the currently clinically used transfected cytokines.
全细胞肿瘤疫苗用于治疗恶性黑色素瘤的效果不一。细胞因子转染的肿瘤细胞作为疫苗在动物模型中已显示出疗效,但需要与增强全身抗肿瘤免疫反应的其他方法进行比较。新一代号称比传统佐剂更有效的免疫佐剂现已可供评估。我们在B16-F10小鼠黑色素瘤模型中研究了一种油微乳佐剂制剂(IDEC抗原制剂(IDEC-AF))的作用。在对全细胞肿瘤疫苗接种方案进行标准化后,我们发现,与单独接种全细胞疫苗的小鼠相比,接种经照射的全细胞与IDEC-AF联合疫苗的小鼠在受到活肿瘤细胞攻击后,肿瘤生长受到显著抑制。IDEC-AF优于两种传统佐剂,即明矾和不完全弗氏佐剂,并且与IL-2转染细胞相比,油微乳佐剂产生的反应更可靠。此外,该佐剂在疗效上与IL-4转染的B16-F10细胞相当。鉴于使用细胞因子转染的肿瘤细胞存在实际困难,且某些细胞因子的治疗范围有限,一种廉价且易于给药的佐剂制剂被证明与目前临床上使用的一些转染细胞因子同样有效或更有效。