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Immunoliposomes

A Promising Approach to Targeting Cancer Therapy

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Abstract

Immunoliposomes (antibody-coupled liposomes) have been regarded as very attractive drug-targeting systems for chemotherapeutic cancer treatment. Fundamental problems regarding immunoliposome preparation and application such as antibody coupling and immunoliposome stability and pharmacokinetics have been overcome during the last decade. Therefore, several promising studies on tumour targeting have been described in recent years. Adding to existing reviews on liposomal drug delivery, this article focuses on immunoliposome tumour targeting and summarises various experiments of immunoliposome application in vitro and in vivo with respect to structural liposomal parameters, therapeutic potential and the requirements of the target sites. New therapeutic trends related to immunoliposomes are also considered. Remaining problems in immunoliposome application, especially immunological aspects, are discussed, as are strategies that might help to overcome these obstacles.

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References

  1. Gregoriadis G, Ryman BE. Fate of protein containing liposomes injected into rats. An approach to the treatment of storage diseases. Eur J Biochem 1972; 24: 485–91

    Article  PubMed  CAS  Google Scholar 

  2. Gregoriadis G, Ryman BE. Lysosomal localization of fructofuranoside-containing liposomes injected into rats. Biochem J 1972; 129: 123–33

    PubMed  CAS  Google Scholar 

  3. Freise J, Mueller WH, Broelsch C, et al. In vivo distribution of liposomes between parenchymal and non-parenchymal cells in rat liver. Biomedicine 1980; 32: 118–23

    PubMed  CAS  Google Scholar 

  4. Roerdink FH, Dijkstra J, Hartman G, et al. The involvement of parenchymal, Kupffer and endothelial liver cells in hepatic uptake of intravenously injected liposomes. Effect of lanthanum and gadolinium salts. Biochim Biophys Acta 1981; 677: 79–89

    Article  PubMed  CAS  Google Scholar 

  5. Kleinerman ES, Murray JL, Synder JS, et al. Activation of tumoricidal properties in monocytes from cancer patients following intravenous administration of liposomes containing muramyl tripeptide phosphatidylethanolamine. Cancer Res 1989; 49: 4665–70

    PubMed  CAS  Google Scholar 

  6. Dinney CP, Bucana CD, Utsugi T, et al. Therapy of spontaneous lung metastasis of murine renal adenocarcinoma by systemic administration of liposomes containing the macrophage activator CGP 31362. Cancer Res 1991; 51: 3741–7

    PubMed  CAS  Google Scholar 

  7. Patel HM. Serum opsonins and liposomes: their interaction and opsonophagocytosis. Crit Rev Ther Drug Carrier Syst 1992; 9: 39–90

    PubMed  CAS  Google Scholar 

  8. Alving CR, Wassef NM. Complement dependent phagocytosis of liposomes: suppression of ’stealth’ lipids. J Liposome Res 1992; 2: 383–95

    Article  CAS  Google Scholar 

  9. Allen TM, Chonn A. Large unilamellar liposomes with low uptake into the reticuloendothelial system. FEBS Lett 1987; 223: 42–6

    Article  PubMed  CAS  Google Scholar 

  10. Klibanov AL, Maruyama K, Torchilin VP, et al. Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett 1990, 268: 235–7

    Article  PubMed  CAS  Google Scholar 

  11. Blume G, Cevc G. Liposomes for the sustained drug release. Biochim Biophys Acta 1990; 1029: 91–7

    Article  PubMed  CAS  Google Scholar 

  12. Torchilin VP. How do polymers prolong circulation time of liposomes? J. Liposome Res 1996; 6: 99–116

    Article  CAS  Google Scholar 

  13. Litzinger DC, Buiting AM, van Rooijen N, et al. Effect of liposome size on the circulation time and intraorgan distribution of amphipathic poly(ethylene glycol)-containing liposomes. Biochim Biophys Acta 1994; 1190: 99–107

    Article  PubMed  CAS  Google Scholar 

  14. Maruyama K, Yuda T, Okamoto A, et al. Effect of molecular weight in amphipathic polyethyleneglycol on prolonging the circulation time of large unilamellar liposomes. Chem Pharm Bull 1991; 39: 1620–2

    Article  PubMed  CAS  Google Scholar 

  15. Klibanov AL, Maruyama K, Beckerleg AM, et al. Activity of amphipathic poly (ethylene glycol) 5000 to prolong the circulation time of liposomes depends on the liposome size and is unfavorable for immunoliposome binding to target. Biochim Biophys Acta 1991; 1062: 142–8

    Article  PubMed  CAS  Google Scholar 

  16. Allen TM. The use of glycolipids and hydrophilic polymers in avoiding rapid uptake of liposomes by the mononuclear phagocyte system. Adv Drug Del Rev 1994; 13: 285–309

    Article  CAS  Google Scholar 

  17. Scherphof GL, Morselt HWM, Allen TM. Intrahepatic distribution of long circulating liposomes containing poly (ethylene glycol) distearoyl phosphatidylethanolamine. J Liposome Res 1994; 4: 213–28

    Article  CAS  Google Scholar 

  18. Jain RK. Vascular and interstitial barriers to delivery of therapeutic agents in tumors. Cancer Metastasis Rev 1990; 9: 253–66

    Article  PubMed  CAS  Google Scholar 

  19. Ishida O, Maruyama K, Sasaki K, et al. Size-dependent extravasation and interstitial localization of polyethyleneglycol liposomes in solid tumor-bearing mice. Int J Pharm 1999; 190: 49–56

    Article  PubMed  CAS  Google Scholar 

  20. Yuan F, Leunig M, Huang SK, et al. Microvascular permeability and interstitial penetration of sterically stabilized (stealth) liposomes in a human tumor xenograft. Cancer Res 1994; 54: 3352–6

    PubMed  CAS  Google Scholar 

  21. Uziely B, Jeffers S, Isacson R, et al. Liposomal doxorubicin: antitumor activity and unique toxicities during complementary phase I studies. J Clin Oncol 1995; 13: 1777–85

    PubMed  CAS  Google Scholar 

  22. Leserman LD, Barbet J, Kourilsky F, et al. Targeting to cells of fluorescent liposomes covalently coupled with monoclonal antibody or protein A. Nature 1980; 288: 602–4

    Article  PubMed  CAS  Google Scholar 

  23. Heath TD, Fraley RT, Papahadjopoulos D. Antibody targeting of liposomes: cell specificity obtained by conjugation of F(ab’)2 to vesicle surface. Science 1980; 210: 539–41

    Article  PubMed  CAS  Google Scholar 

  24. Derksen JTP, Morselt HWM, Scherphof GL. Uptake and processing of immunoglobulin-coated liposomes by subpopulations of rat liver macrophages. Biochim Biophys Acta 1988; 971: 127–36

    Article  PubMed  CAS  Google Scholar 

  25. Mori A, Klibanov AL, Torchilin VP, et al. Influence of the steric barrier activity of amphipathic poly (ethyleneglycol) and ganglioside GM1 on the circulation time of liposomes and on the target binding of immunoliposomes in vivo. FEBS Lett 1991; 284: 263–6

    Article  PubMed  CAS  Google Scholar 

  26. Allen TM, Hansen CB, Zalipsky S. Antibody-targeted stealth liposomes. In: Lasic D, Martin F, editors. Stealth liposomes. Boca Raton: CRC Press, 1995: 233–44

    Google Scholar 

  27. Hansen CB, Kao GY, Moase EH, et al. Attachment of antibodies to sterically stabilized liposomes: evaluation, comparison and optimization of coupling procedures. Biochim Biophys Acta 1995; 1239: 133–44

    Article  PubMed  Google Scholar 

  28. Maruyama K, Takizawa T, Yuda T, et al. Targetability of novel immunoliposomes modified with amphipathic poly (ethylene glycol)s conjugated at their distal terminals to monoclonal antibodies. Biochim Biophys Acta 1995; 1234: 74–80

    Article  PubMed  Google Scholar 

  29. Zalipsky S. Synthesis of end-group functionalized polyethylene glycol-lipid conjugates for preparation of polymer-grafted liposomes. Bioconj Chem 1993; 4: 296–9

    Article  CAS  Google Scholar 

  30. Allen TM, Brandeis E, Hansen CB, et al. A new strategy for attachment of antibodies to sterically stabilized liposomes resulting in efficient targeting to cancer cells. Biochim Biophys Acta 1995; 1237: 99–108

    Article  PubMed  Google Scholar 

  31. Bendas G, Krause A, Bakowsky U, et al. Targetability of novel immunoliposomes prepared by a new antibody conjugation technique. Int J Pharm 1999; 81: 79–93

    Article  Google Scholar 

  32. Allen TM, Agrawal AK, Ahmad I, et al. Antibody-mediated targeting of long-circulating (Stealth®) liposomes. J Liposome Res 1994; 4: 1–25

    Article  CAS  Google Scholar 

  33. Kirpotin W, Park JW, Hong K, et al. Sterically stabilized anti HER-2 immunoliposomes: design and targeting to human breast cancer cells in vitro. Biochemistry 1997; 36: 66–75

    Article  PubMed  CAS  Google Scholar 

  34. Maruyama K, Takahashi N, Tagawa T, et al. Immunoliposomes bearing polyethyleneglycol-coupled Fab’fragment show prolonged circulation time and high extravasation into targeted solid tumors in vivo. FEBS Lett 1997; 413: 177–80

    Article  PubMed  CAS  Google Scholar 

  35. Phillips NC, Gagne L, Tsoukas C, et al. Immunoliposome targeting to murine CD4+ leukocytes is dependent on immune status. J Immunol 1994; 152: 3168–74

    PubMed  CAS  Google Scholar 

  36. Phillips NC, Dahman J. Immunogenicity of immunoliposomes: reactivity against species-specific IgG and liposomal phospholipids. Immunol Lett 1995; 45: 149–52

    Article  PubMed  CAS  Google Scholar 

  37. Harding JA, Engbers CM, Newman MS, et al. Immunogenicity and pharmacokinetic attributes of poly (ethylene glycol)-grafted immunoliposomes. Biochim Biophys Acta 1997; 1327: 181–92

    Article  PubMed  CAS  Google Scholar 

  38. Keinanen K, Laukkanen ML. Biosynthetic lipid-tagging of antibodies. FEBS Lett 1994; 346: 123–6

    Article  PubMed  CAS  Google Scholar 

  39. Laukkanen ML, Alfthan K, Keinanen K. Functional immunoliposomes harboring a biosynthetically lipid-tagged single-chain antibody. Biochemistry 1994; 33: 11664–70

    Article  PubMed  CAS  Google Scholar 

  40. De Kruif J, Storm G, van Bloois L, et al. Biosynthetically lipidmodified human scFv fragments from phage display libraries as targeting molecules for immunoliposomes. FEBS Lett 1996; 399: 232–6

    Article  PubMed  Google Scholar 

  41. Ahmad I, Allen TM. Antibody-mediated specific binding and cytotoxicity of liposome-entrapped doxorubicin to lung cancer cells in vitro. Cancer Res 1992; 52: 4817–20

    PubMed  CAS  Google Scholar 

  42. Park JW, Hong K, Carter P, et al. Development of anti-p185 HER-2 immunoliposomes for cancer therapy. Proc Natl Acad Sci USA 1995; 92: 1327–31

    Article  PubMed  CAS  Google Scholar 

  43. Koning GA, Gorter A, Scherphof GL, et al. Antiproliferative effect of immunoliposomes containing 5-fluorodeoxyuridine-dipalmitate on colon cancer cells. Br J Cancer 1999; 80: 1718–25

    Article  PubMed  CAS  Google Scholar 

  44. Koning GA, Morselt HW, Velinova MJ, et al. Selective transfer of a lipophilic prodrug of 5-fluorodeoxyuridine from immunoliposomes to colon cancer cells. Biochim Biophys Acta 1999; 1420: 153–67

    Article  PubMed  CAS  Google Scholar 

  45. Maruyama K, Kennel SJ, Huang L. Lipid composition is important for highly efficient target binding and retention of immunoliposomes. Proc Natl Acad Sci USA 1990; 87: 5744–8

    Article  PubMed  CAS  Google Scholar 

  46. Nam SM, Kim HS, Ahn WS, et al. Sterically stabilized anti GM3, anti Lex immunoliposomes: targeting to B16BL6, HRT-18 cancer cells. Oncology Res 1999; 11: 9–16

    CAS  Google Scholar 

  47. Emanuel N, Kedar E, Bolotin EM, et al. Targeted delivery of doxorubicin via sterically stabilized immunoliposomes: pharmacokinetic and biodistribution in tumor-bearing mice. Pharm Res 1996; 13: 861–8

    Article  PubMed  CAS  Google Scholar 

  48. Park JW, Hong K, Kirpotin DB, et al. Anti HER-2 immunoliposomes for targeted therapy of human tumors. Cancer Lett 1997; 118: 153–60

    Article  PubMed  CAS  Google Scholar 

  49. Vingerhoeds MH, Steerenberg PA, Hendriks JJ, et al. Immunoliposome-mediated targeting of doxorubicin to human ovarian carcinoma in vitro and in vivo. Br J Cancer 1996; 74: 1023–9

    Article  PubMed  CAS  Google Scholar 

  50. Ahmad I, Longenecker M, Samuel J, et al. Antibody-targeted delivery of doxorubicin-entrapped in sterically stabilized liposomes can eradicate lung cancer in mice. Cancer Res 1993; 53: 1484–8

    PubMed  CAS  Google Scholar 

  51. Lopez de Menezes DE, Pilarski LM, Allen TM. In vitro and in vivo targeting of immunoliposomal doxorubicin to human B-cell lymphoma. Cancer Res 1998; 58: 3320–30

    Google Scholar 

  52. Vingerhoeds MH, Haisma HJ, Belliot SO, et al. Immunoliposomes as enzyme-carriers (immuno-enzymosomes) for antibody-directed enzyme prodrug therapy (ADEPT): optimization of prodrug activating capacity. Pharm Res 1996; 13: 604–10

    Article  PubMed  CAS  Google Scholar 

  53. Pagnan G, Stuart DD, Pastorino F, et al. Delivery of c-myb antisense oligodeoxynucleotides to human neuroblastoma cells via disialoganglioside GD (2)-targeted immunoliposomes: antitumor effect. J Natl Cancer Inst 2000; 92: 253–61

    Article  PubMed  CAS  Google Scholar 

  54. Shi N, Pardridge WM. Noninvasive gene targeting to the brain. Proc Natl Acad Sci USA 2000; 97: 7567–72

    Article  PubMed  CAS  Google Scholar 

  55. Pagnan G, Montaldo PG, Pastorino F, et al. GD2-mediated melanoma cell targeting and cytotoxicity of liposome-entrapped fenretinide. Int J Cancer 1999; 81: 268–74

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Gerd Bendas.

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Bendas, G. Immunoliposomes. BioDrugs 15, 215–224 (2001). https://doi.org/10.2165/00063030-200115040-00002

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