Skip to main content
Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1988 Jun;26(3):222–230. doi: 10.1007/BF00199933

Parameters involved in the enhancement of monoclonal antibody targeting in vivo with recombinant interferon

Fiorella Guadagni 1, Jeffrey Schlom 1, Susan Pothen 1, Sidney Pestka 2, John W Greiner 1,
PMCID: PMC11038564  PMID: 3383205

Abstract

The effects of recombinant human leukocyte (clone A) interferon (rHu-IFN-αA) were investigated on the expression of monoclonal antibody (MAb)-defined tumor antigens expressed on human mammary and colon carcinomas. The rHu-IFN-αA treatment substantially increased the localization of radiolabeled MAb B6.2-F(ab′)2 to the transplantable Clouser human mammary carcinoma, as well as to the moderately differentiated human colon xenograft WiDr, when grown as s.c. tumors in athymic mice. In contrast, human tumor cell lines (i.e., LS174T, A375, etc.) that were unresponsive to the antigen-augmenting ability of rHu-IFN-αA in vitro were also unresponsive in vivo, indicating a possible method of screening carcinoma cell populations for subsequent rHu-IFN-αA adjuvant therapy prior to MAb administration. The method of delivery of rHu-IFN-αA was also studied. The i.m. route resulted in a 3–4 h plasma half-life for rHu-IFN-αA. The administration of rHu-IFN-αA via an osmotic pump resulted in a stable circulating plasma titer of 400–800 antiviral units/ml for 7 days. Utilizing delivery of rHu-IFN-αA by the constant infusion route, it was found that the increase in localization of 125I-B6.2-F(ab′)2 was dependent on (1) the length of time of treatment and (2) the circulating plasma rHu-IFN-αA levels. These results thus provide information useful for subsequent studies to determine the potential efficacy of adjuvant rHu-IFN-αA treatment for MAb-targeted tumor diagnosis and treatment.

Keywords: Interferon, Colon Carcinoma, Mammary Carcinoma, Human Tumor Cell Line, Constant Infusion

References

  • 1.Barnstable CJ, Bodmer WF, Brown G, Galfre G, Milstein C, Williams AF, Ziegler A. Production of monoclonal antibodies to group A erythrocytes, HLA and other human surface antigens — new tools for genetic analysis. Cell. 1978;14:9. doi: 10.1016/0092-8674(78)90296-9. [DOI] [PubMed] [Google Scholar]
  • 2.Colcher D, Horan Hand P, Nuti M, Schlom J. A spectrum of monoclonal antibodies reactive with human mammary tumor cells. Proc Natl Acad Sci USA. 1981;78:3199. doi: 10.1073/pnas.78.5.3199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Colcher D, Zalutsky M, Kaplan W, Kufe D, Austin F, Schlom J. Radiolocalization of human mammary tumors in athymic mice by a monoclonal antibody. Cancer Res. 1983;43:736. [PubMed] [Google Scholar]
  • 4.Colcher D, Esteban JM, Carrasquillo JA, Sugarbaker P, Reynolds JC, Bryant G, Larson SM, Schlom J. Quantitative analysis of selective radiolabeled monoclonal antibody localization in metastatic lesions of colorectal cancer patients. Cancer Res. 1987;14:1185. [PubMed] [Google Scholar]
  • 5.Epenetos AA, Britton KE, Mather S, Shephard J, Granowska M, Taylor-Papadimitriou J, Nimmon CC, Durbin H, Hawkins LR, Malpas JS, Bodmer WF. Targeting of iodine-123 labeled tumor-associated monoclonal antibodies to ovarian, breast and gastrointestinal tumors. Lancet. 1982;II:999. doi: 10.1016/s0140-6736(82)90046-0. [DOI] [PubMed] [Google Scholar]
  • 6.Evinger M, Rubinstein M, Pestka S. Antiproliferative and antiviral activities of human leukocyte interferons. Arch Biochem Biophys. 1981;210:319. doi: 10.1016/0003-9861(81)90195-8. [DOI] [PubMed] [Google Scholar]
  • 7.Fellous M, Kamoun M, Gresser I, Bono R. Enhanced expression of HLA antigens and B2-microglobulin on interfer-on-treated human lymphoid cells. Eur J Immunol. 1979;9:446. doi: 10.1002/eji.1830090606. [DOI] [PubMed] [Google Scholar]
  • 8.Giacomini P, Aguzzi A, Tecce R, Fisher PB, Ferrone S. Modulation by recombinant DNA leukocyte (α) and fibroblast (β) interferons of the expression and shedding of HLA and tumor associated antigens by human melanoma cells. J Immunol. 1984;133:1649. [PubMed] [Google Scholar]
  • 9.Giovanella BC, Stehlin JS, Williams LS, Lee SS, Shepard RC. Heterotransplantation of human cancers into nude mice. Cancer. 1978;42:2269. doi: 10.1002/1097-0142(197811)42:5<2269::aid-cncr2820420527>3.0.co;2-f. [DOI] [PubMed] [Google Scholar]
  • 10.Goeddel DU, Yelverton E, Ullrich A, Heyneker HL, Miozzari G, Holmes W, Seesburg PH, Dull T, May L, Stebbing N, Crea R, Maeda S, McCordliss R, Sloma A, Taber TM, Gross M, Familletti PC, Pestka S. Human leukocyte interferon produced by E. coli is biologically active. Nature. 1980;287:411. doi: 10.1038/287411a0. [DOI] [PubMed] [Google Scholar]
  • 11.Greiner JW. Modulation of antigen expression in human tumor cell populations. Cancer Invest. 1986;4:239. doi: 10.3109/07357908609018454. [DOI] [PubMed] [Google Scholar]
  • 12.Greiner JW, Horan Hand P, Noguchi P, Fisher PB, Pestka S, Schlom J. Enhanced expression of surface tumor-associated antigens on human breast and colon tumor cells after recombinant human leukocyte α-interferon treatment. Cancer Res. 1984;44:3208. [PubMed] [Google Scholar]
  • 13.Greiner JW, Guadagni F, Pestka S, Schlom J. Interferon as cell growth inhibitors and antitumor factors. New York: Alan R. Liss; 1985. Augmentation of antigen expression by recombinant human interferon; p. 17. [Google Scholar]
  • 14.Greiner JW, Tobi M, Fisher PB, Langer JA, Pestka S. Differential responsiveness of cloned mammary carcinoma cell populations to human recombinant alpha interferon mediated enhancement of tumor antigen expression. Int J Cancer. 1985;36:159. doi: 10.1002/ijc.2910360206. [DOI] [PubMed] [Google Scholar]
  • 15.Greiner JW, Fisher PB, Pestka S, Schlom J. Differential effects of recombinant human leukocyte interferons on cell surface antigen expression. Cancer Res. 1986;46:4984. [PubMed] [Google Scholar]
  • 16.Greiner JW, Horan Hand P, Wunderlich D, Colcher D. Radioimmunoassay for detection of changes in cell surface antigen expression induced by interferon. Methods Enzymol. 1986;119:682. doi: 10.1016/0076-6879(86)19091-4. [DOI] [PubMed] [Google Scholar]
  • 17.Greiner JW, Schlom J, Pestka S, Langer JA, Giacomini P, Kusama M, Ferrone S, Fisher PB. Modulation of tumor associated antigen expression and shedding by recombinant human leukocyte and fibroblast interferons. Pharmacol Ther. 1987;31:209. doi: 10.1016/0163-7258(85)90023-3. [DOI] [PubMed] [Google Scholar]
  • 18.Greiner JW, Guadagni F, Noguchi P, Pestka S, Colcher D, Fisher PB, Schlom J. Recombinant interferon enhances monoclonal antibody targeting of carcinoma lesions in vivo. Science. 1987;235:895. doi: 10.1126/science.3580039. [DOI] [PubMed] [Google Scholar]
  • 19.Greiner JW, Pestka S, Fisher PB, Schlom J. Augmentation of surface antigens on human carcinoma cells by recombinant leukocyte interferon. In: Baron S, editor. The interferon system: a current review. Austin, TX: University of Texas Press; 1988. [Google Scholar]
  • 20.Gutterman JU, Fine S, Quesada J, Horning SJ, Levine JF, Alexanian R, Bernhardt L, Kramer M, Spiegel H, Collrum W, Troun P, Merigan T, Dziewanowski Z. Recombinant leukocyte A interferon: pharmacokinetics single-dose tolerance, and biological effects in cancer patients. Ann Intern Med. 1982;96:549. doi: 10.7326/0003-4819-96-5-549. [DOI] [PubMed] [Google Scholar]
  • 21.Hayes DF, Zalutsky MR, Kaplan W, Noska M, Thor A, Colcher D, Kufe DW. Pharmacokinetics of radiolbeled monoclonal antibody B6.2 in patients with metastatic breast cancer. Cancer Res. 1986;46:3157. [PubMed] [Google Scholar]
  • 22.Horan Hand P, Colcher D, Salomon D, Ridge J, Noguchi P, Schlom J. Influence of spatial configuration of carcinoma cell populations on the expression of a tumor-associated glycoprotein. Cancer Res. 1985;45:833. [PubMed] [Google Scholar]
  • 23.Johnson VG, Schlom J, Paterson AJ, Bennett J, Magnani JL, Colcher D. Analysis of a human tumor-associated glycoprotein (TAG-72) identified by monoclonal antibody B72.3. Cancer Res. 1986;46:850. [PubMed] [Google Scholar]
  • 24.Johnston WW, Szpak CA, Lottich CS, Thor A, Schlom J. Use of a monoclonal antibody (B72.3) as an immunocytochemical adjunct to diagnosis of adenocarcinoma in human effusions. Cancer Res. 1985;45:1894. [PubMed] [Google Scholar]
  • 25.Kufe DW, Nadler L, Sargent L, Shapiro H, Hand P, Austin F, Colcher D, Schlom J. Biological behavior of human breast carcinoma-associated antigen expressed during cellular proliferation. Cancer Res. 1983;43:851. [PubMed] [Google Scholar]
  • 26.Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970;227:680. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  • 27.Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265. [PubMed] [Google Scholar]
  • 28.Mach J-P, Buchegger F, Forni M, Ritschard J, Bercher C, Lumbroso J-D, Schreyer M, Girardet C, Accola RS, Carrel S. Use of radiolabeled monoclonal anti-CEA antibodies for the detection of human carcinoma by external photoscanning and tomoscintigraphy. Immunol Today. 1981;2:239. doi: 10.1016/0167-5699(81)90011-6. [DOI] [PubMed] [Google Scholar]
  • 29.Maeda S, McCordliss R, Gross M, Sloma A, Familletti PC, Tabor J, Evinger M, Levy WP, Pestka S. Construction and identification of bacterial plasmids containing nucleotide sequence for human leukocyte interferon. Proc Natl Acad Sci USA. 1980;77:7010. doi: 10.1073/pnas.77.12.7010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Martin SE, Moshiri S, Thor A, Vilasi V, Chu EW, Schlom J. Identification of adenocarcinoma in cytospin preparations of effusions using monoclonal antibody B72.3. Am J Clin Pathol. 1986;86:10. doi: 10.1093/ajcp/86.1.10. [DOI] [PubMed] [Google Scholar]
  • 31.Moldofsky PJ, Powe J, Mulhern CB, Jr, Hammond N, Sears HF, Gatenby RA, Steplewski Z, Koprowski H. Metastatic colon carcinoma detected with radiolabeled F(ab′)2 monoclonal antibody fragments. Radiology. 1983;149:549. doi: 10.1148/radiology.149.2.6622704. [DOI] [PubMed] [Google Scholar]
  • 32.Muraro R, Wunderlich D, Thor A, Lundy J, Noguchi P, Cunningham R, Schlom J. Definition of monoclonal antibodies of a repertoire of epitopes on carcinoembryonic antigen differentially expressed in human colon carcinomas versus normal adult tissues. Cancer Res. 1985;45:5769. [PubMed] [Google Scholar]
  • 33.Nuti M, Teramoto YA, Mariani-Constantini R, Horan Hand P, Colcher D, Schlom J. A monoclonal antibody (B72.3) defines patterns of distribution of a novel tumor-associated antigen in a human mammary carcinoma cell population. Int J Cancer. 1982;29:539. doi: 10.1002/ijc.2910290509. [DOI] [PubMed] [Google Scholar]
  • 34.Nuti M, Mottolese M, Viora M, Donnorso RP, Schlom J, Natali PG. Use of monoclonal antibodies to human breast tumor-associated antigens in fine needle aspirate cytology. Int J Cancer. 1986;37:493. doi: 10.1002/ijc.2910370404. [DOI] [PubMed] [Google Scholar]
  • 35.Ortaldo JR, Herberman RB, Harvey C, Osheroff P, Pan YE, Kelder B, Pestka S. A species of human interferon that lacks the ability to boost human natural killer activity. Proc Natl Acad Sci USA. 1984;81:4926. doi: 10.1073/pnas.81.15.4926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Rowlinson G, Balkwill F, Snook D, Hooker G, Epenetos AA. Enhancement by γ-interferon of in vivo tumor radiolocalization by a monoclonal antibody against HLA-DR antigen. Cancer Res. 1986;46:6413. [PubMed] [Google Scholar]
  • 37.Sahagan BG, Dorai H, Saltygaber-Muller J, Tonegazza F, Guidon CA, Lilly SP, McDonald KW, Morrissey DV, Stone BA, Davis GL, McIntosh PK, Moore GP. A genetically engineered murine/human chimeric antibody retains specificity for human tumor-associated antigen. J Immunol. 1986;137:1066. [PubMed] [Google Scholar]
  • 38.Schlom J, Greiner JW, Horan-Hand P, Colcher D, Inghirami G, Weeks M, Pestka S, Fisher PB, Kufe DW. Human breast cancer markers defined by monoclonal antibodies. In: Sell S, Reisfeld R, editors. Monoclonal antibodies in cancer. Clifton, NJ: Humana Press; 1985. p. 247. [Google Scholar]
  • 39.Spear GT, Paulnock DM, Jordan R, Hawkins MJ, Borden EC. Modulation of human peripheral blood monocyte HLA-DR expression by recombinant IFN-γ. Proc Am Assoc Cancer Res. 1985;26:277. [Google Scholar]
  • 40.Staehlin T, Hobbs DS, Kung H-F, Lai C-Y, Pestka S. Purification and characterization of recombinant human leukocyte interferon (IFLrA) with monoclonal antibodies. J Biol Chem. 1981;256:2750. [PubMed] [Google Scholar]
  • 41.Studier WF. Analysis of bacteriophage T7 early RNAs and proteins on slab gels. J Mol Biol. 1973;79:237. doi: 10.1016/0022-2836(73)90003-x. [DOI] [PubMed] [Google Scholar]
  • 42.Thor A, Ohuchi N, Szpak CA, Johnston WW, Schlom J. Distribution of oncofetal antigen tumor-associated glycoprotein-72 defined by monoclonal antibody B72.3. Cancer Res. 1986;46:3118. [PubMed] [Google Scholar]
  • 43.Tran R, Horan Hand P, Greiner JW, Pestka S, Schlom J. Enhancement of surface antigen expression on human breast carcinoma cell by recombinant human interferons. J Interferon Res. 1988;8:75. doi: 10.1089/jir.1988.8.75. [DOI] [PubMed] [Google Scholar]
  • 44.Ziai MR, Imberti L, Tongson A, Ferrone S. Differential modulation by recombinant immune interferon of the expression and shedding of HLA antigen and melanoma associated antigens by a melanoma cell line resistant to the antiproliferative activity of immune interferon. Cancer Res. 1985;45:5877. [PubMed] [Google Scholar]

Articles from Cancer Immunology, Immunotherapy : CII are provided here courtesy of Springer

RESOURCES