Abstract
Human recombinant gamma interferon (INF-γ) activated human peripheral blood monocytes to a cytotoxic state capable of lysing adherent tumorigenic cells without harming normal cells. The efficiency of INF-γ activation of monocytes is enhanced by encapsulating INF-γ within liposomes: The minimum effective dose (MED) of free INF-γ for monocyte activation was found to be 1–10 U/ml, per 105 monocytes, whereas the minimum dose for INF-γ encapsulated in liposomes was less than 0.0025 U. Monocytes treated with liposome-encapsulated INF-γ retained their cytotoxic phenotype for much longer than do monocytes treated with free INF-γ. Since liposomes can be passively targeted to cells of the reticuloendothelial system following IV administration, these findings suggest that liposome-encapsulated INF-γ may have therapeutic potential that should be evaluated in vivo.
Keywords: Interferon, Normal Cell, Human Blood, Therapeutic Potential, Human Peripheral Blood
References
- 1.Alving CR. Therapeutic potential of liposomes as drug carriers in leishmaniasis, malaria, and vaccines. In: Gregoridis G, Senior J, Trovet A, editors. Targeting of drugs. New York: Plenum; 1982. pp. 373–353. [Google Scholar]
- 2.Anderson P, Yip VK, Vilcek J. Human interferon-γ is internalized and degraded by cultured fibroblasts. J Biol Chem. 1983;258:6579. [PubMed] [Google Scholar]
- 3.Bourgeade MF, Chany C, Merigan TC. Type I and type II interferons: differential actions in transformed cells. J Gen Virol. 1980;46:449. doi: 10.1099/0022-1317-46-2-449. [DOI] [PubMed] [Google Scholar]
- 4.Branca AA, Baglioni C. Evidence that types I and II interferons have different receptors. Nature. 1981;294:768. doi: 10.1038/294768a0. [DOI] [PubMed] [Google Scholar]
- 5.Cameron DJ, Churchill WH. Cytotoxicity of human macrophage for tumor cells: Enhancement by human lymphocyte mediators. J Clin Invest. 1979;63:977. doi: 10.1172/JCI109398. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Catalona WJ, Ratliff TL, McCool RE. Gamma interferon induced by S aureus protein augments natural killing and ADCC. Nature. 1981;291:77. doi: 10.1038/291077a0. [DOI] [PubMed] [Google Scholar]
- 7.Churchill WH, Jr, Piessens WF, Sulis CA, David JR. Macrophages activated as suspension cultures with lymphocyte mediators devoid of antigen become cytotoxic for tumor cells. J Immunol. 1975;115:781. [PMC free article] [PubMed] [Google Scholar]
- 8.Dean RT, Virelizier JL. Interferon as a macrophage activating factor. I. Enchancement of cytotoxicity by fresh and matured human monocytes in the absence of other soluble signals. Clin Exp Immunol. 1983;51:501. [PMC free article] [PubMed] [Google Scholar]
- 9.Dianzani F, Zucca M, Scupham A, Georgiades JA. Immune and virus-induced interferons may activate cells by different derepressional mechanisms. Nature. 1980;283:400. doi: 10.1038/283400a0. [DOI] [PubMed] [Google Scholar]
- 10.Fidler IJ. Activation in vitro of mouse macrophages by syngeneic, allogeneic, or xenogeneic lymphocyte supernatants. J Natl Cancer Inst. 1975;55:1159. doi: 10.1093/jnci/55.5.1159. [DOI] [PubMed] [Google Scholar]
- 11.Fidler IJ. Therapy of spontaneous metastases by intravenous injection of liposomes containing lymphokines. Science. 1980;208:1469. doi: 10.1126/science.7384789. [DOI] [PubMed] [Google Scholar]
- 12.Fidler IJ, Raz A. The induction of tumoricidal capacities in mouse and rat macrophages by lymphokines. In: Pick E, editor. Lymphokines, vol. 3. New York: Academic; 1981. pp. 345–363. [Google Scholar]
- 13.Fidler IJ, Raz A, Fogler WE, Hoyer LC, Poste G. The role of plasma membrane receptors and the kinetics of macrophage activation by lymphokines encapsulated in liposomes. Cancer Res. 1981;41:495. [PubMed] [Google Scholar]
- 14.Fidler IJ, Barnes Z, Fogler WE, Kirsh R, Bugelski P, Poste G. Involvement of macrophages in the eradication of established metastases following intravenous injection of liposomes containing macrophage activators. Cancer Res. 1982;42:496. [PubMed] [Google Scholar]
- 15.Fogler WE, Raz A, Fidler IJ. In situ activation of murine macrophages by liposomes containing lymphokines. Cell Immunol. 1980;53:214. doi: 10.1016/0008-8749(80)90440-2. [DOI] [PubMed] [Google Scholar]
- 16.Gray PW, Leung DW, Pennica D, Yelverton E, Najarian R, Simonsen CC, Derynck R, Sherwood PJ, Wallace DM, Berger SL, Levinson AD, Goeddel DV. Expression of human immune interferon C DNA in E. coli and monkey cells. Nature. 1982;295:503. doi: 10.1038/295503a0. [DOI] [PubMed] [Google Scholar]
- 17.Graybill JR, Cravin PC, Taylor RL, Williams DM, Magge WE. Treatment of murine cryptococcosis with liposome-associated amphotericin B. J Infect Dis. 1982;145:748. doi: 10.1093/infdis/145.2.748. [DOI] [PubMed] [Google Scholar]
- 18.Gregoriadis G, Allison AC. Liposomes in biological systems. New York: Wiley Interscience; 1980. [Google Scholar]
- 19.Izadkhah Z, Mandel AD, Sonnenfeld G. Effect of treatment of mice with sera containing gamma interferon on the course of infections with Salmonella typhimurium strain LT-2. J Interferon Res. 1980;1:137. doi: 10.1089/jir.1980.1.137. [DOI] [PubMed] [Google Scholar]
- 20.Kende M, Schroit AJ, Rill W, Canonico P. Treatment of Rift Valley fever virus-infected Swiss mice with liposome encapsulated muramyl dipeptide. Las Vegas: ICAAC; 1983. p. 108. [Google Scholar]
- 21.Kleinerman ES, Schroit AJ, Fogler WE, Fidler IJ. Tumoricidal activity of human monocytes activated in vitro by free and liposome encapsulated human lymphokines. J Clin Invest. 1983;72:304. doi: 10.1172/JCI110970. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Kleinerman ES, Zickt R, Wiltrout RH, Fidler IJ. A human macrophage activating factor distinct from γ-interferon. Proc Am Assoc Cancer Res. 1984;25:261. [Google Scholar]
- 23.Koff WC, Showalter SD, Seniff DA, Hampar B. Lysis of herpesvirus-infected cells by macrophages activated with free or liposome-encapsulated lymphokine produced by a murine T cell hybridoma. Infect Immun. 1983;42:1067. doi: 10.1128/iai.42.3.1067-1072.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Koff WC, Fidler IJ, Showalter SD, Chakrabarty MK, Hampar B, Ceccorulli LM, Kleinerman ES. Human monocytes activated by immunomodulators in liposomes lyse herpesvirus-infected but not normal cells. Science. 1984;224:1007. doi: 10.1126/science.6426057. [DOI] [PubMed] [Google Scholar]
- 25.Le J, Prensky W, Yip YK, Chang Z, Hoffman T, Stevenson HC, Balazs I, Sadlik JR, Vilcek J. Activation of human monocyte cytotoxicity by natural and recombinant immune interferon. J Immunol. 1983;131:2821. [PubMed] [Google Scholar]
- 26.Mantovani A, Dean JH, Jerrells TR, Herberman RB. Augmentation of tumoricidal activity of human monocytes and macrophages by lymphokines. Int J Cancer. 1980;25:691. doi: 10.1002/ijc.2910250602. [DOI] [PubMed] [Google Scholar]
- 27.Nathan CF, Murray HW, Wiebe ME, Rubin BY. Identification of interferon — γ as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med. 1983;158:670. doi: 10.1084/jem.158.3.670. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Pfefferkorn ER, Guyre PM. Recombinant human gamma interferon blocks the growth of Toxoplasma gondii in cultured human fibroblasts. Fed Proc. 1983;42:964. [Google Scholar]
- 29.Poste G, Kirsch R, Fogler W, Fidler IJ. Activation of tumoricidal properties in mouse macrophages by lymphokines encapsulated in liposomes. Cancer Res. 1979;39:881. [PubMed] [Google Scholar]
- 30.Poste G, Bucana C, Raz A, Bugelski P, Kirsh R, Fidler IJ. Analysis of the fate of systemically administered liposomes and implications for their use in drug delivery. Cancer Res. 1982;42:1412. [PubMed] [Google Scholar]
- 31.Rubin BY, Gupta SL. Differential efficacies of human type I and type II interferons as antiviral and antiproliferative agents. Proc Natl Acad Sci USA. 1980;77:5928. doi: 10.1073/pnas.77.10.5928. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 32.Rucco LP, Meltzer MS. Macrophage activation for tumoricidal macrophages by supernatants of PPD-stimulated Bacillus Calmette-Guerin-immune spleen cells cultures. J Immunol. 1977;119:889. [PubMed] [Google Scholar]
- 33.Schroit AJ, Hart IR, Madsen J, Fidler IJ. Selective delivery of drugs encapsulated in liposomes: natural targeting to macrophages involved in various disease states. J Biol Resp Modif. 1983;2:97. [PubMed] [Google Scholar]
- 34.Schroit AJ, Galligioni E, Fidler IJ. Factors influencing the in situ activation of macrophages by liposomes containing muramyl dipeptide. Biol Cell. 1983;47:87. [Google Scholar]
- 35.Shirahata T, Shimizu K. Production and properties of immune interferon from spleen cell cultures of toxoplasma-infected mice. Microbiol Immunol. 1980;24:1109. doi: 10.1111/j.1348-0421.1980.tb02915.x. [DOI] [PubMed] [Google Scholar]
- 36.Stewart WE III, editor. The interferon system. 2nd edn. New York: Springer; 1981. [Google Scholar]
- 37.Taramelli D, Holden HT, Varesio L. Endotoxin requirement for macrophage activation by lymphokines in a rapid microcytotoxicity assay. J Immunol Methods. 1980;37:225. doi: 10.1016/0198-8859(81)90040-9. [DOI] [PubMed] [Google Scholar]