Abstract
Recombinant adenoviral mediated delivery of suicide and cytokine genes has been investigated as a treatment for hepatic metastases of colon carcinoma in mice. Liver tumors were established by intrahepatic implantation of a poorly immunogenic colon carcinoma cell line (MCA-26), which is syngeneic in BALB/c mice. Intratumoral transfer of the herpes simplex virus type 1 thymidine kinase (HSV-tk) and the murine interleukin (mIL)-2 genes resulted in substantial hepatic tumor regression, induced an effective systemic antitumoral immunity in the host and prolonged the median survival time of the treated animals from 22 to 35 days. The antitumoral immunity declined gradually, which led to tumor recurrence over time. A recombinant adenovirus expressing the mIL-12 gene was constructed and tested in the MCA-26 tumor model. Intratumoral administration of this cytokine vector alone increased significantly survival time of the animals with 25% of the treated animals still living over 70 days. These data indicate that local expression of IL-12 may also be an attractive treatment strategy for metastatic colon carcinoma.
Full text
PDFImages in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bett A. J., Haddara W., Prevec L., Graham F. L. An efficient and flexible system for construction of adenovirus vectors with insertions or deletions in early regions 1 and 3. Proc Natl Acad Sci U S A. 1994 Sep 13;91(19):8802–8806. doi: 10.1073/pnas.91.19.8802. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bramson J., Hitt M., Gallichan W. S., Rosenthal K. L., Gauldie J., Graham F. L. Construction of a double recombinant adenovirus vector expressing a heterodimeric cytokine: in vitro and in vivo production of biologically active interleukin-12. Hum Gene Ther. 1996 Feb 10;7(3):333–342. doi: 10.1089/hum.1996.7.3-333. [DOI] [PubMed] [Google Scholar]
- Brunda M. J., Luistro L., Hendrzak J. A., Fountoulakis M., Garotta G., Gately M. K. Role of interferon-gamma in mediating the antitumor efficacy of interleukin-12. J Immunother Emphasis Tumor Immunol. 1995 Feb;17(2):71–77. doi: 10.1097/00002371-199502000-00001. [DOI] [PubMed] [Google Scholar]
- Brunda M. J., Luistro L., Warrier R. R., Wright R. B., Hubbard B. R., Murphy M., Wolf S. F., Gately M. K. Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J Exp Med. 1993 Oct 1;178(4):1223–1230. doi: 10.1084/jem.178.4.1223. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Caruso M., Panis Y., Gagandeep S., Houssin D., Salzmann J. L., Klatzmann D. Regression of established macroscopic liver metastases after in situ transduction of a suicide gene. Proc Natl Acad Sci U S A. 1993 Aug 1;90(15):7024–7028. doi: 10.1073/pnas.90.15.7024. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen S. H., Chen X. H., Wang Y., Kosai K., Finegold M. J., Rich S. S., Woo S. L. Combination gene therapy for liver metastasis of colon carcinoma in vivo. Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2577–2581. doi: 10.1073/pnas.92.7.2577. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chen S. H., Shine H. D., Goodman J. C., Grossman R. G., Woo S. L. Gene therapy for brain tumors: regression of experimental gliomas by adenovirus-mediated gene transfer in vivo. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3054–3057. doi: 10.1073/pnas.91.8.3054. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Corbett T. H., Griswold D. P., Jr, Roberts B. J., Peckham J. C., Schabel F. M., Jr Tumor induction relationships in development of transplantable cancers of the colon in mice for chemotherapy assays, with a note on carcinogen structure. Cancer Res. 1975 Sep;35(9):2434–2439. [PubMed] [Google Scholar]
- D'Andrea A., Rengaraju M., Valiante N. M., Chehimi J., Kubin M., Aste M., Chan S. H., Kobayashi M., Young D., Nickbarg E. Production of natural killer cell stimulatory factor (interleukin 12) by peripheral blood mononuclear cells. J Exp Med. 1992 Nov 1;176(5):1387–1398. doi: 10.1084/jem.176.5.1387. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davidson R. L., Kaufman E. R., Crumpacker C. S., Schnipper L. E. Inhibition of herpes simplex virus transformed and nontransformed cells by acycloguanosine: mechanisms of uptake and toxicity. Virology. 1981 Aug;113(1):9–19. doi: 10.1016/0042-6822(81)90132-x. [DOI] [PubMed] [Google Scholar]
- Eastham J. A., Chen S. H., Sehgal I., Yang G., Timme T. L., Hall S. J., Woo S. L., Thompson T. C. Prostate cancer gene therapy: herpes simplex virus thymidine kinase gene transduction followed by ganciclovir in mouse and human prostate cancer models. Hum Gene Ther. 1996 Mar 1;7(4):515–523. doi: 10.1089/hum.1996.7.4-515. [DOI] [PubMed] [Google Scholar]
- Elion G. B. The biochemistry and mechanism of action of acyclovir. J Antimicrob Chemother. 1983 Sep;12 (Suppl B):9–17. doi: 10.1093/jac/12.suppl_b.9. [DOI] [PubMed] [Google Scholar]
- Fang B., Eisensmith R. C., Li X. H., Finegold M. J., Shedlovsky A., Dove W., Woo S. L. Gene therapy for phenylketonuria: phenotypic correction in a genetically deficient mouse model by adenovirus-mediated hepatic gene transfer. Gene Ther. 1994 Jul;1(4):247–254. [PubMed] [Google Scholar]
- Furman P. A., McGuirt P. V., Keller P. M., Fyfe J. A., Elion G. B. Inhibition by acyclovir of cell growth and DNA synthesis of cells biochemically transformed with herpesvirus genetic information. Virology. 1980 Apr 30;102(2):420–430. doi: 10.1016/0042-6822(80)90109-9. [DOI] [PubMed] [Google Scholar]
- Gately M. K., Warrier R. R., Honasoge S., Carvajal D. M., Faherty D. A., Connaughton S. E., Anderson T. D., Sarmiento U., Hubbard B. R., Murphy M. Administration of recombinant IL-12 to normal mice enhances cytolytic lymphocyte activity and induces production of IFN-gamma in vivo. Int Immunol. 1994 Jan;6(1):157–167. doi: 10.1093/intimm/6.1.157. [DOI] [PubMed] [Google Scholar]
- Gately M. K., Wolitzky A. G., Quinn P. M., Chizzonite R. Regulation of human cytolytic lymphocyte responses by interleukin-12. Cell Immunol. 1992 Aug;143(1):127–142. doi: 10.1016/0008-8749(92)90011-d. [DOI] [PubMed] [Google Scholar]
- Graham F. L., Smiley J., Russell W. C., Nairn R. Characteristics of a human cell line transformed by DNA from human adenovirus type 5. J Gen Virol. 1977 Jul;36(1):59–74. doi: 10.1099/0022-1317-36-1-59. [DOI] [PubMed] [Google Scholar]
- Hashimoto W., Takeda K., Anzai R., Ogasawara K., Sakihara H., Sugiura K., Seki S., Kumagai K. Cytotoxic NK1.1 Ag+ alpha beta T cells with intermediate TCR induced in the liver of mice by IL-12. J Immunol. 1995 May 1;154(9):4333–4340. [PubMed] [Google Scholar]
- Heufler C., Koch F., Stanzl U., Topar G., Wysocka M., Trinchieri G., Enk A., Steinman R. M., Romani N., Schuler G. Interleukin-12 is produced by dendritic cells and mediates T helper 1 development as well as interferon-gamma production by T helper 1 cells. Eur J Immunol. 1996 Mar;26(3):659–668. doi: 10.1002/eji.1830260323. [DOI] [PubMed] [Google Scholar]
- Kobayashi M., Fitz L., Ryan M., Hewick R. M., Clark S. C., Chan S., Loudon R., Sherman F., Perussia B., Trinchieri G. Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J Exp Med. 1989 Sep 1;170(3):827–845. doi: 10.1084/jem.170.3.827. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lamont A. G., Adorini L. IL-12: a key cytokine in immune regulation. Immunol Today. 1996 May;17(5):214–217. doi: 10.1016/0167-5699(96)30011-x. [DOI] [PubMed] [Google Scholar]
- Martinotti A., Stoppacciaro A., Vagliani M., Melani C., Spreafico F., Wysocka M., Parmiani G., Trinchieri G., Colombo M. P. CD4 T cells inhibit in vivo the CD8-mediated immune response against murine colon carcinoma cells transduced with interleukin-12 genes. Eur J Immunol. 1995 Jan;25(1):137–146. doi: 10.1002/eji.1830250124. [DOI] [PubMed] [Google Scholar]
- Nastala C. L., Edington H. D., McKinney T. G., Tahara H., Nalesnik M. A., Brunda M. J., Gately M. K., Wolf S. F., Schreiber R. D., Storkus W. J. Recombinant IL-12 administration induces tumor regression in association with IFN-gamma production. J Immunol. 1994 Aug 15;153(4):1697–1706. [PubMed] [Google Scholar]
- Naume B., Gately M., Espevik T. A comparative study of IL-12 (cytotoxic lymphocyte maturation factor)-, IL-2-, and IL-7-induced effects on immunomagnetically purified CD56+ NK cells. J Immunol. 1992 Apr 15;148(8):2429–2436. [PubMed] [Google Scholar]
- Nishiyama Y., Rapp F. Anticellular effects of 9-(2-hydroxyethoxymethyl) guanine against herpes simplex virus-transformed cells. J Gen Virol. 1979 Oct;45(1):227–230. doi: 10.1099/0022-1317-45-1-227. [DOI] [PubMed] [Google Scholar]
- O'Malley B. W., Jr, Chen S. H., Schwartz M. R., Woo S. L. Adenovirus-mediated gene therapy for human head and neck squamous cell cancer in a nude mouse model. Cancer Res. 1995 Mar 1;55(5):1080–1085. [PubMed] [Google Scholar]
- Pardoll D. M. Paracrine cytokine adjuvants in cancer immunotherapy. Annu Rev Immunol. 1995;13:399–415. doi: 10.1146/annurev.iy.13.040195.002151. [DOI] [PubMed] [Google Scholar]
- Ram Z., Culver K. W., Walbridge S., Blaese R. M., Oldfield E. H. In situ retroviral-mediated gene transfer for the treatment of brain tumors in rats. Cancer Res. 1993 Jan 1;53(1):83–88. [PubMed] [Google Scholar]
- Robertson M. J., Soiffer R. J., Wolf S. F., Manley T. J., Donahue C., Young D., Herrmann S. H., Ritz J. Response of human natural killer (NK) cells to NK cell stimulatory factor (NKSF): cytolytic activity and proliferation of NK cells are differentially regulated by NKSF. J Exp Med. 1992 Mar 1;175(3):779–788. doi: 10.1084/jem.175.3.779. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rossi A. R., Pericle F., Rashleigh S., Janiec J., Djeu J. Y. Lysis of neuroblastoma cell lines by human natural killer cells activated by interleukin-2 and interleukin-12. Blood. 1994 Mar 1;83(5):1323–1328. [PubMed] [Google Scholar]
- Sgadari C., Angiolillo A. L., Tosato G. Inhibition of angiogenesis by interleukin-12 is mediated by the interferon-inducible protein 10. Blood. 1996 May 1;87(9):3877–3882. [PubMed] [Google Scholar]
- Short M. P., Choi B. C., Lee J. K., Malick A., Breakefield X. O., Martuza R. L. Gene delivery to glioma cells in rat brain by grafting of a retrovirus packaging cell line. J Neurosci Res. 1990 Nov;27(3):427–439. doi: 10.1002/jnr.490270322. [DOI] [PubMed] [Google Scholar]
- Soiffer R. J., Robertson M. J., Murray C., Cochran K., Ritz J. Interleukin-12 augments cytolytic activity of peripheral blood lymphocytes from patients with hematologic and solid malignancies. Blood. 1993 Nov 1;82(9):2790–2796. [PubMed] [Google Scholar]
- Tahara H., Zeh H. J., 3rd, Storkus W. J., Pappo I., Watkins S. C., Gubler U., Wolf S. F., Robbins P. D., Lotze M. T. Fibroblasts genetically engineered to secrete interleukin 12 can suppress tumor growth and induce antitumor immunity to a murine melanoma in vivo. Cancer Res. 1994 Jan 1;54(1):182–189. [PubMed] [Google Scholar]
- Takeda K., Seki S., Ogasawara K., Anzai R., Hashimoto W., Sugiura K., Takahashi M., Satoh M., Kumagai K. Liver NK1.1+ CD4+ alpha beta T cells activated by IL-12 as a major effector in inhibition of experimental tumor metastasis. J Immunol. 1996 May 1;156(9):3366–3373. [PubMed] [Google Scholar]
- Trinchieri G. Interleukin-12 and its role in the generation of TH1 cells. Immunol Today. 1993 Jul;14(7):335–338. doi: 10.1016/0167-5699(93)90230-I. [DOI] [PubMed] [Google Scholar]
- Vagliani M., Rodolfo M., Cavallo F., Parenza M., Melani C., Parmiani G., Forni G., Colombo M. P. Interleukin 12 potentiates the curative effect of a vaccine based on interleukin 2-transduced tumor cells. Cancer Res. 1996 Feb 1;56(3):467–470. [PubMed] [Google Scholar]
- Voest E. E., Kenyon B. M., O'Reilly M. S., Truitt G., D'Amato R. J., Folkman J. Inhibition of angiogenesis in vivo by interleukin 12. J Natl Cancer Inst. 1995 Apr 19;87(8):581–586. doi: 10.1093/jnci/87.8.581. [DOI] [PubMed] [Google Scholar]
- Wolf S. F., Temple P. A., Kobayashi M., Young D., Dicig M., Lowe L., Dzialo R., Fitz L., Ferenz C., Hewick R. M. Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells. J Immunol. 1991 May 1;146(9):3074–3081. [PubMed] [Google Scholar]
- Zitvogel L., Tahara H., Robbins P. D., Storkus W. J., Clarke M. R., Nalesnik M. A., Lotze M. T. Cancer immunotherapy of established tumors with IL-12. Effective delivery by genetically engineered fibroblasts. J Immunol. 1995 Aug 1;155(3):1393–1403. [PubMed] [Google Scholar]