Carrier and adjuvant properties of liposome-borne tumor-specific antigens

Abstract

The purpose of this study was to examine (1) the association of tumor extract proteins with phospholipid vesicles of varying physiochemical properties, and (2) the adjuvant and carrier properties of liposome-borne tumor antigens in the in vivo induction of an antitumor immune response. Cell surface antigens of the 3-methylcholanthrene-induced fibrosarcoma of C3H/HeJ mice, MCA-F, were extracted using 2.5% 1-butanol. Crude and electrofocused antigen preparations capable of eliciting a protective antitumor immune response were used to prepare liposome vaccines. The incorporation of extract proteins into liposomes formed by butanol dialysis (BVD) was three- to five-fold greater than the encapsulation of protein into the aqueous compartment of multilamellar vesicles (MLV). The electrochemical properties of the BDV had a significant effect on the induction of an antitumor response: Antigens borne on negatively charged, but not uncharged, liposomes were effective in protecting hosts against supralethal tumor challenge, and displayed a specific activity 20- to 50-fold greater than soluble antigen. Antigens carried by MLV were not effective in generating an immunoprotective response. The lipophilic characteristics of butanol-extracted antigens allowed (1) the passive adsorption of immunoprotective tumor antigen onto the surface of preformed vesicles, and (2) adsorption of MCA-F antigen onto the surface of an antigenically distinct tumor MCA-D. In the latter experiment, adsorption of MCA-F-specific antigen onto MCA-D cells resulted in a change in the membrane antigen phenotype as measured by indirect immunofluorescence. Although butanol released a lipophilic moiety from cells which spontaneously reassociated with phospholipid bilayers, no evidence for a lipoidal antigen was obtained when tumor-derived lipids were used as immunogens. This study demonstrates that butanol-extracted tumor antigen is lipophilic without being a lipid, and that negatively charged liposomes can be effective as carriers and adjuvants for tumor antigens in the induction of an antitumor immune response.

Reconstituted membranes of tumour cells (proteoliposomes) induce specific protection to murine lymphoma cells

“…Antigens that are presented on cell membranes or on membrane-like structures (e. g. liposomes) are usually more immunogenic than antigens in "soluble form". For instance, LeGrue [19] reported that a partially purified butanol extract adsorbed to liposomes displayed a specific activity 20-to 50-fold greater than the soluble antigen. Moreover, the immunogenicity of liposome-associated antigens is affected by the characteristics of the liposomes (e. g. charge, fluidity, mode of antigen incorporation) and also by the presence of adjuvants, co-incorporated with the antigen in the same liposome preparation [ 12].…”

Critical factors for liposome-incorporated tumour-associated antigens to induce protective tumour immunity to SL2 lymphoma cells in mice

“…Second, the protein-to-PL ratio may affect the immunogenicity of liposome-presented antigens, as described for the humoral response against protein antigens [10,38]. Liposomal incorporation of crude or semi-purified TAA extracts can augment specific immune reactions against TAA [16,25,30,33,34]. In these studies a variety of tumour models, extraction techniques, and liposome types has been employed.…”

Medical Application of Liposomes

“…Because liposomes are biodegradable, have little toxicity, are not immunogenic, and may target specific certain cells in vivo, they are advantageous as immunological adjuvants. 12 For improving the immunogenic potential of a specific antigen, such as glycolipids, proteins, and antigens to dangerous viruses, among others, liposomes are effective adjuvants. During in vivo tests antibody-sensitized liposomes, which have frequently shown highly positive outcomes in in-vitro investigations that frequently take place without macrophages, immunoglobulins, or components of the complement system, failed.…”