Reconstituted membranes of tumour cells (proteoliposomes) induce specific protection to murine lymphoma cells.
Antigens presented on cell membranes or on liposomes are usually more immunogenic than antigens in soluble form, this being one of the reasons for the weak immunogenicity of extracted tumour-associated transplantation antigens (TATA). The main objective of this study is to solubilize TATA from tumour cells and to present them on a membrane-like structure to the immune system. Crude tumour cell membranes of SL2 lymphosarcoma cells (a spontaneously arising, weakly immunogenic tumour) were solubilized with octylglucoside or sodium deoxycholate, and reconstituted membranes (proteoliposomes) were prepared by detergent removal. Mice immunized s.c. with reconstituted membranes were protected against an i.p. challenge with tumour cells. Although octylglucoside solubilized only 41% of the membrane proteins, the reconstituted membranes were as immunoprotective as crude membranes. (Glyco)proteins were probably the major membrane components in the reconstituted membranes that induce immunoprotection, as mice immunized with preparations constituted of (glyco)lipids from SL2 cells could not reject SL2 cells. If Freund's complete adjuvant was used with the first immunization injection, no potentiation of the elicited immune responses was observed. Besides the membrane TATA, SL2 cells contained an apparently non-membrane-bound TATA, which was found in the cytoplasm. It is concluded that detergent solubilization of membranes and subsequent preparation of reconstituted membranes can be used to obtain membrane tumour-associated antigens that retain activity for induction of protective tumour immunity. The major advantage of this method is that membrane proteins are solubilized and are subsequently presented on a membrane-like structure that resembles the tumour cell membrane. On theoretical and practical grounds it provides a promising alternative for whole-cell vaccines.
Bergers
J J
JJ
Department of Pharmaceutics, Faculty of Pharmacy, University of Utrecht, The Netherlands.
Den Otter
W
W
De Groot
J W
JW
De Blois
A W
AW
Dullens
H F
HF
Steerenberg
P A
PA
Crommelin
D J
DJ
D000818:Animals; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000276:immunology*; D002462:Cell Membrane / Q000737:chemistry / Q000276:immunology; D003840:Deoxycholic Acid / Q000737:chemistry; D003902:Detergents / Q000737:chemistry; D005960:Glucosides / Q000737:chemistry; D008223:Lymphoma / Q000276:immunology* / Q000517:prevention & control; D008563:Membrane Lipids / Q000276:immunology; D051379:Mice; D008811:Mice, Inbred DBA; D011510:Proteolipids / Q000276:immunology*; D016019:Survival Analysis
D000951:Antigens, Neoplasm; D003902:Detergents; D005960:Glucosides; D008563:Membrane Lipids; D011510:Proteolipids; C020485:proteoliposomes; D003840:Deoxycholic Acid; C018619:octyl-beta-D-glucoside