Abstract
Irradiated tumor cells genetically modified to secrete granulocyte/macrophage-colony-stimulating factor (GM-CSF tumor vaccine) are potent stimulators of systemic antitumor immunity. For the preparation of a GM-CSF gene-modified tumor vaccine, it is important to achieve efficient genetic transduction of tumor cells, leading to an appropriate expression of the induced gene. In this report, with a view to developing a protocol for an effective cancer vaccination therapy, we examined the vaccination efficacies of tumor cells secreting GM-CSF by either adenovirus-or retrovirus-mediated genetic transduction. By using an adenoviral vector, Adex1CAmGMCSF, a highly efficient gene were achieved. Unexpectedly, animal vaccination studies showe that the GM-CSF tumor vaccine transduced with the Adex1CAmGMCSF recombinant adenovirus (adenoviral GM-CSF tumor vaccine) was less efficacious than that transduced with the MFGmGMCSF recombinant retrovirus (retroviral GM-CSF tumor vaccine). The GM-CSF serum concentration attained by the adenoviral GM-CSF tumor vaccine was much higher than that obtained by the retroviral GM-CSF tumor vaccine. Our findings indicate that an optimal level of GM-CSF production is important for the tumor vaccine to elicit an adequate response in the host antitumor immunity.
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Abbreviations
- GM-CSF :
-
granulocyte/macrophage-colony-stimulating factor
- IL-2 :
-
interleukin-2
- TNF :
-
tumor necrosis factor
References
Abe J, Wakimoto H, Nakamura Y, Kanegae Y, Saito I, Aoyagi M, Hirakawa K, Hamada H (1994) Immunogene therapy for cancer by cytokine gene-modified tumor vaccine and tumor-infiltrating lymphocytes (TIL). Cancer Gene Ther 1:312
Abe J, Wakimoto H, Nakamura Y, Aoyagi M, Hirakawa K, Hamada H (1995) Cytokine gene-modified tumor vaccination intensified by a streptococcal preparation OK432. Cancer Immunol Immunother (in press)
Anderson WF (1994) Gene therapy for cancer. Hum Gene Ther 5:1–2
Aoki T, Tashiro K, Miyatake S, Kinashi T, Nakano T, Oda Y, Kikuchi H, Honjo T. (1992) Expression of murine interleukin 7 in a murine glioma cell line results in reduced tumorigenicity in vivo. Proc Natl Acad Sci USA 89:3850–3854
Asher AL, Mulé JJ, Kasid A, Restifo NP, Solo JC, Reichert CM, Jaffe G, Fendly B, Kriegler M, Rosenberg SA (1991) Murine tumor cells transduced with the gene for tumor necrosis factor-α. J Immunol 146:3227–3234
Attia MAM, Weiss DW (1966) Immunology of spontaneous mammary carcinomas in mice V. Acquired tumor resistance and enhancement in strain A mice infected with mammary tumor virus. Cancer Res 26:1787–1800
Chen Lk Ashe S, Brady WA, Hellström I, Hellström KE, Ledbetter JA, McGowan P, Linsley PS (1992) Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. Cell 71:1093–1102
Colombo MP, Forni G (1994) Cytokine gene transfer in tumor inhibition and tumor therapy: where are we now? Immunol Today 15:48–51
Connor J, Bannerji R, Saito S, Heston W, Fair W, Gilboa E (1993) Regression of bladder tumors in mice treated with interleukin 2 gene-modified tumor cells. J Exp Med 177:1127–1134
Danos O, Mulligan, RC (1988) Safe and efficient generation of recombinant retroviruses with amphotropic and ecotropic host ranges. Proc Natl Acad Sci USA 85:6460–6464
Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, Jackson V, Hamada H, Pardoll D, Mulligan RC (1993) Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA 90:3539–3543
Fearon ER, Pardoll DM, Itaya T, Golumbek P, Levitsky HI, Simons JW, Karasuyama H, Vogelstein B, Frost P (1990) Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell 60:397–403
Fidler IJ (1975) Biological behavior of malignant melanoma cells correlated to their survival in vivo. Cancer Res 35:218–224
Gansbacher B, Zier K, Daniels B, Cronin K, Bannerji R, Gilboa E (1990a) Interleukin 2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity. J Exp Med 172:1217–1224
Gansbacher B, Bannerji R, Daniels B, Zier K, Cronin K, Gilboa E (1990b) Retroviral vector-mediated γ-interferon gene transfer into tumor cells generates potent and long lasting antitumor immunity. Cancer Res 50:7820–7825
Golumbek PT, Lazenby AJ, Levitsky HI, Jaffee LM, Karasuyama H, Baker M, Pardoll DM (1991) Treatment of established renal cancer by tumor cells engineered to secrete interleukin-4. Science 254:713–716
Hanada K, Wakimoto H, Abe J, Orimoto K, Nakamura Y, Murata M, Hayashi M, Hamada H (1994) Strategies for immunogene therapy against cancer. Proc Nagoya Int Symp Cancer Chemother 9:73–80
Hamada H (1994)_Tumor vaccines expressing cytokine genes: combination with adoptive immunogene therapy for cancer. Proc Hiroshima Cancer Semin 4:17–20
Nakamura Y, Wakimoto H, Abe J, Kanagae Y, Saito I, Aoyagi M, Hirakawa K, Hamada H (1994) Adoptive immunotherapy with murine tumor-specific T lymphocytes engineered to secrete interleukin-2. Cancer Res 54:5757–5760
Niwa H, Yamamura K, Miyazaki J (1991) Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene 108:193–200
Pardoll DM (1993) Cancer vaccines. Immunol Today 14:310–316
Porgador A, Tzehoval E, Katz A, Vadai E, Revel M, Feldman M, Eisenbach L (1992) Interleukin-6 gene transfection into Lewis lung carcinoma tumor cells suppresses the malignant phenotype and confers immunotherapeutic competence against parental metastatic cells. Cancer Res 52:3679–3686
Porgador A, Bannerji R, Watanabe Y, Feldman M, Gilboa E, Eisenbach L (1993) Antimetastatic vaccination of tumor-bearing mice with two types of IFN-γ gene-inserted tumor cells. J Immunol 150:1458–1470
Saito I, Oya Y, Yamamoto K, Yuasa T, Shimojo H (1985) Construction of nondefective adenovirus type 5 bearing a 2.8-kilobase hepatitis B virus DNA near the right end of its genome. J Virol 54:711–719
Saito S, Bannerji R, Gansbacher B, Rosenthal FM, Romanenko P, Heston WDW, Fair WR, Gilboa E (1994) Immunotherapy of bladder cancer with cytokine gene-modified tumor vaccines. Cancer Res 54:3516–3520
Sanda MG, Ayyagari SR, Jaffee EM, Epstein JI, Clift SL, Cohen LK, Dranoff G, Pardoll DM, Mulligan RC, Simons JW (1994) Dernonstration of a rational strategy for human prostate cancer gene therapy. J Urol 151:622–628
Schmidt W, Schweighoffer T, Herbst E, Berger M, Schilcher F, Schaffner G, Birnstiel M (1995) Cancer vaccines: The interleukin 2 dosage effect. Proc Natl Acad Sci USA 92:4711–4714
Tepper RI, Mulé JJ (1994) Experimental and clinical studies of cytokine gene-modified tumor cells. Hum Gene Ther 5:153–164
Tepper RI, Pattengale PK, Leder P (1989) Murine interleukin-4 displays potent anti-tumor activity in vivo. Cell 57:503–512
Townsend SE, Allison JP (1993) Tumor rejection after direct costimulation of CD8+ T cells by B7-transfected melanoma cells. Science 259:368–370
Vieweg J, Rosenthal FM, Bannerji R, Heston WDW, Fair WR, Gansbacher B, Gilboa E (1994) Immunotherapy of prostate cancer in the Dunning rat model: use of cytokine gene modified tumor vaccines. Cancer Res 54:1760–1765
Wakimoto H, Abe J, Nakamura Y, Kanegae Y, Saito I, Aoyagi M, Hirakawa K, Hamada H (1994) Enhanced antitumor effects by vaccines and IL-2-secreting cytotoxic T lymphocytes. Gene Therapy, Cold Spring Harbor Laboratory, Cold Spring Harbor NY, p 164
Yamaguchi S, Wakimoto H, Yoshida H (1995) Enhancement of retrovirus-mediated gene transduction efficiency by transient overexpression of the amphotropic receptor, GLVR2. Nucleic Acids Res 23:2080–2081
Yang G, Hellström KE, Hellström I, Chen L (1995) Antitumor immunity elicited by tumor cells transfected with B7-2, a second ligand for CD28/CTLA-4 costimulatory molecules. J Immunol 154:2794–2800
Zatloukal K, Schneeberger A, Berger M, Schmidt W, Koszik F, Kutil R, Cotten M, Wagner E, Buschle M, Maass G, Payer E, Stingl G, Birnstiel ML (1995) Elicitation of a systemic and protective antimelanoma immune response by an IL-2-based vaccine. J Immunol 154:3406–3419
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Work dedicated to Dr. Haruo Sugano on the occasion of his 70th birthday. The material of this paper was essentially presented at the 60th Anniversary Symposium of the Cancer Institute and the Cancer Institute Hospital, Tokyo, held in September 1994
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Abe, J., Wakimoto, H., Yoshida, Y. et al. Antitumor effect induced by granulocyte/macrophage-colony-stimulating factor gene-modified tumor vaccination: Comparison of adenovirus- and retrovirus-mediated genetic transduction. J Cancer Res Clin Oncol 121, 587–592 (1995). https://doi.org/10.1007/BF01197775
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DOI: https://doi.org/10.1007/BF01197775