Effective tumor immunization induced by cells of elevated membrane-lipid microviscosity.

Abstract

The immunogenicity of a series of mouse tumor lines propagated in vivo (T [thymus-derived] and B [bone marrow-derived] 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 i.p. into syngeneic mice. A 2nd 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. In over 90% of the mice 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. [Three of the tumors used were induced by 7,12-dimethylbenz[a]anthracene and designated 38-C-54, 38-C-13 and 38-C-38. They were a T-cell lymphoma, B-cell lymphoma and a mammary adenocarcinoma, respectively. The other 2 tumors were the ALC ascitic lymphoblastic tumor and T-lymphoma D-Rad LV. They were both induced with radiation leukemia virus variant D-Rad LV.].