<i>In vivo</i> induction of tumor‐specific immunity by glycolipid extracts of SV40‐transformed cells

Ansel, Sandra; Blangy, Daniel

doi:10.1002/ijc.2910340419

Cited by 7 publications

(4 citation statements)

References 19 publications

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“…Also purified glycolipids incorporated into liposomes were not immunoprotective. Tumour-associated glycolipid antigens have been shown to elicit specific immune responses in animal models and in cancer patients [31,33], but only some occasional reports demonstrate that immunization with glycolipids can induce protective tumour immunity [1].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, glycolipids were purified from SL2 cells and separated into neutral and acidic fractions. In order to make them more immunogenic, these glycolipids were incorporated into liposomes [1,23]. Mice were immunized with "free" glycolipids or with glycolipids in liposomes employing a similar immunizaüon schedule.…”

Section: Potential Of Membrane Lipids To Induce Protective Tumour Immmentioning

confidence: 99%

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

Bergers

Otter

Groot

et al. 1992

Cancer Immunol Immunother

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Potential Of Membrane Lipids To Induce Protective Tumour Immmentioning

confidence: 99%

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

Bergers

Otter

Groot

et al. 1992

Cancer Immunol Immunother

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“…Several methods have been used to augment the immunogenicity of tumor-associated antigens by introducing exogenous immunogenic determinants to the surface of tumor cells [1,13,28,31,47]. Heterogenization of tumor by viruses is one such approach [12,43,44].…”

Section: Introductionmentioning

confidence: 99%

Active specific immunotherapy with vaccinia colon oncolysate enhances the immunomodulatory and antitumor effects of interleukin-2 and interferon α in a murine hepatic metastasis model

Arroyo

Bash

Wallack

1990

Cancer Immunol Immunother

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The role of cytokines as primary or adjuvant antineoplastic agents has been well established. Interleukin-2 (IL-2) and the interferons have, particularly, proven to be effective antitumor agents when given alone, and seem to act synergistically on the eradication of metastases from immunogenic tumors. Active specific immunotherapy, in the form of viral oncolysates, has also shown effectiveness in cancer therapy. Bearing this in mind, we decided to combine these agents in an adjuvant triple regimen and compare their effectiveness to other treatments in terms of tumor burden and survival in a murine colon cancer hepatic metastases model. BALB/c mice were injected with CC-36, a weakly immunogenic murine colon adenocarcinoma, intrasplenically, to produce artificial liver metastases. The animals were divided into one control group and seven treatment groups receiving either vaccinia colon oncolysate (VCO), IL-2, interferon-alpha (IFN alpha) alone, or combinations of these agents. Half the animals were followed for survival and the other half were sacrificed at the end of the experiment for quantification of tumor burden. The blood of the sacrificed animals was utilized in a series of immunological tests in order to demonstrate the cytolytic potential of the peripheral blood lymphocytes (PBL) in each treatment group, as well as to characterize phenotypically the cells acting as effectors. The triple-adjuvant regimen group was by far the most effective treatment group, demonstrating 100% survival and a significant reduction in tumor burden when compared to other groups. Furthermore, the PBL from the animals in this group showed 69.4% lysis of the CC-36 target cells in vitro. These effector lymphocytes were characterized as ASMG1-/Lyt2.2+ cytolytic lymphocytes. We conclude that these lymphocytes were stimulated by the administration of VCO and further augmented by the immunomodulation of the cytokines given in the triple regimen, and that such a regimen might prove beneficial in the treatment of established hepatic metastases from weakly immunogenic tumors.

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“…Thus, they are attractive for studies of natural or induced host immunity to autologous (syngeneic) tumors. In vivo tumor immunity can be specifically induced with glycolipid extracts from SV-40 transformed cells as demonstrated by resistance to challenge with viable tumor isografts (Ansel and Blangy, 1984). Antibody responses to the ganglioside GM, have been induced in melanoma patients using purified glycolipid (Livingston et al, 1987) or a preparation from melanoma cells (Tai er al., 1985).…”

mentioning

confidence: 99%

Monoclonal antibodies to glycolipids of the isoglobo‐series detect tumor‐associated antigens in rats

Brodin

Thurin

Karlsson

et al. 1989

Intl Journal of Cancer

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Monoclonal antibodies (MAbs) directed to 2 neutral glycolipids, isoglobotetraosylceramide and a 6-sugar isogloboneolactoseries hybrid glycolipid, previously shown to be enriched in rat colorectal tumor tissue, were produced by immunization with purified glycolipids. Four MAbs were selected which demonstrate 3 different specificity patterns when tested for binding to purified and crude preparations of neutral glycolipids, cultured tumor cells and fibroblasts and frozen tissue sections. MAbs 14.2 and 14.10, but not 14.3, stained most epithelial colorectal carcinomas, rat testis and a subpopulation of cells in the rat gastric mucosa. However, all 3 MAbs showed strong staining and binding to sections and cultured clones of the cytokeratin-negative tumor of colorectal origin, which was originally used for preparation of the glycolipid immunogens. The observed difference between MAbs 14.2/10 and MAb 14.3 could not be explained by differences in binding to the 2 original glycolipids used for screening. However, MAbs 14.2/10 were demonstrated to bind to high-molecular-weight glycoprotein(s) (HMW-gp's) previously shown to carry determinants for syngeneic antibodies and extracted from epithelial colorectal tumor tissue after extensive lipid extraction. This suggests that a protein-bound carbohydrate determinant, with similarities to the oligosaccharide part of the isoglobo-series glycolipids, is responsible for this cross-reactivity. The staining of rat testis could be explained by the strong expression in this tissue of glycolipids with 8-10 sugar residues bound by the 14.2/10 but not 14.3 MAbs. The cell-surface expression of the 6-sugar hybrid glycolipid was demonstrated by complement-dependent cytotoxicity and immunofluorescent staining of viable cells.

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In vivo induction of tumor‐specific immunity by glycolipid extracts of SV40‐transformed cells

Cited by 7 publications

References 19 publications

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

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

Active specific immunotherapy with vaccinia colon oncolysate enhances the immunomodulatory and antitumor effects of interleukin-2 and interferon α in a murine hepatic metastasis model

Monoclonal antibodies to glycolipids of the isoglobo‐series detect tumor‐associated antigens in rats

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