Shinitzky M, Skornick Y, Haran-Ghera N
Proc Natl Acad Sci U S A. 1979 Oct;76(10):5313-6. doi: 10.1073/pnas.76.10.5313.
The immunogenicity of a series of mouse tumor lines propagated in vivo (T and B lymphomas and mammary adenocarcinoma) was tested after alteration of the cell membrane-lipid microviscosity. Tumor cells used for immunization were first treated to alter the lipid content, then irradiated and injected intraperitoneally into syngeneic mice. A second identical immunization was performed 14 days later. The degree of immunization in the treated mice was assessed by survival time after challenge with untreated viable tumor cells of the same origin as the immunizing cells. For all tumors tested, enrichment of the immunizing cells with cholesterol or cholesteryl hemisuccinate, which increased the membrane-lipid microviscosity significantly, afforded a marked increase in immunization, compared to that obtained with cells that were only irradiated. Furthermore, in over 90% of the mice that were pretreated with cholesteryl hemisuccinate-enriched cells, tumor growth after the challenge was not detectable. Because the lipid-modifying treatments of the immunizing cells involve no toxic substances, these results may provide the basis for a potent approach to immunotherapy of human cancer.
在改变细胞膜脂质微粘度后,对一系列在体内传代的小鼠肿瘤细胞系(T和B淋巴瘤以及乳腺腺癌)的免疫原性进行了测试。用于免疫的肿瘤细胞首先经过处理以改变脂质含量,然后进行辐照并腹腔注射到同基因小鼠体内。14天后进行第二次相同的免疫。通过用与免疫细胞同源的未处理活肿瘤细胞攻击后小鼠的存活时间来评估处理过的小鼠的免疫程度。对于所有测试的肿瘤,用胆固醇或半琥珀酸胆固醇酯富集免疫细胞,这会显著增加膜脂质微粘度,与仅经过辐照的细胞相比,免疫程度有显著提高。此外,在超过90%用富含半琥珀酸胆固醇酯的细胞预处理的小鼠中,攻击后未检测到肿瘤生长。由于免疫细胞的脂质修饰处理不涉及有毒物质,这些结果可能为人类癌症免疫治疗的有效方法提供基础。