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

  • Original Articles
  • Tumour Vaccine, Liposomes, Reconstituted Membranes, Lymphoma Cells
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Physical and immunogenic properties of reconstituted membranes designed for the presentation of tumour-associated antigens (TAA) to the immune system are described. Proteins and lipids of crude membranes of SL2 murine lymphosarcoma cells were partially solubilized with octylglucoside. Reconstituted membranes, consisting mainly of unilamellar vesicles with a diameter of 0.03–0.15 μm, were formed by detergent removal and were purified by floatation in a discontinuous sucrose gradient to remove non-lipid-bound protein. Subcutaneous immunization of syngeneic mice with reconstituted membranes or with purified reconstituted membranes induced protection against an intraperitoneal challenge with 103 viable SL2 cells. Reconstituted membranes were more immunogenic than crude membranes in immunoprotection experiments when compared on the basis of protein dose. Detergent removal was required to obtain an immunogenic presentation form of SL2 membrane antigens and to avoid toxicity associated with the detergent. Reconstitution of SL2 membranes in the presence of exogenous phospholipid slightly increased the fraction of protein that associated with the reconstituted membranes. However, the immunogenicity of the solubilized membrane TAA was not significantly affected by the presence of exogenous phospholipid. The reconstitution procedure described may be useful in identifying membrane factors required for the induction of immune responses against TAA. The versatility of the system may be employed to develop safe alternatives for whole-cell vaccines.

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Author notes

  1. Joep J. Bergers

    Present address: Department of Clinical Microbiology, Erasmus University, P. O. Box 1738, 3000 DR, Rotterdam, The Netherlands

Authors and Affiliations

  1. Department of Pharmaccutics, Faculty of Pharmacy, University of Utrecht, P. O. Box 80.082, 3508 TB, Utrecht, The Netherlands

    Joep J. Bergers, Monique W. H. Mimpen & Daan J. A. Crommelin

  2. Department of Pathology, University Hospital Utrecht, P. O. Box 85.500, 3508 GA, Utrecht, The Netherlands

    Willem Den Otter, Hub F. J. Dullens & Jan Willem De Groot

  3. Laboratory for Pathology, National Institute of Public Health and Environmental Protection, P. O. Box 1, 3720 BA, Bilthoven, The Netherlands

    Peter A. Steerenberg

Authors
  1. Joep J. Bergers
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  3. Hub F. J. Dullens
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  4. Jan Willem De Groot
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  6. Monique W. H. Mimpen
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  7. Daan J. A. Crommelin
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Bergers, J.J., Den Otter, W., Dullens, H.F.J. et al. Critical factors for liposome-incorporated tumour-associated antigens to induce protective tumour immunity to SL2 lymphoma cells in mice. Cancer Immunol Immunother 37, 271–279 (1993). https://doi.org/10.1007/BF01518522

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  • DOI: https://doi.org/10.1007/BF01518522

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