Abstract
Antigen-loaded dendritic cells (DC) are considered potent stimulators of protective immunity. In some studies, DC hybridized with tumor cells have shown promising antitumor responses in mice as well as in humans. A practical drawback of this approach is the limited availability of autologous tumor samples. We investigated the possibility of hybridizing allogeneic prostate cancer cells with human-monocyte-derived DC, and thereby combine the wide repertoire of antigens from the tumor cells with the costimulatory features of the autologous antigen-presenting cells. Three tumor cell lines were used for hybridization using polyethylene glycol (PEG). We show that all three cell lines formed hybrids with DC to the same extent and without significant loss of viability. Restimulation of autologous T cells with these hybrids resulted in generation of tumor-specific IFNγ-producing T cells with all three tumor cell lines. Similar tumor specificity could not be obtained if T cells were stimulated using a mixture of non-PEG-fused tumor cells and DC. Moreover, these T cells were capable of specific recognition of other tumor cells of prostate cancer origin and autologous DC pulsed with lysate from these prostate cancer cell lines, while a panel of unrelated EBV-transformed B cell lines were not recognized. These results are strongly indicative of the true tumor specificity of these T cells. Our results suggest that DC hybridized with allogeneic prostate cancer cell lines are potent stimulators of a broad prostate-tumor-specific response.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Garrido F, Algarra I. MHC antigens and tumor escape from immune surveillance. Adv Cancer Res 2001; 83:117–158.
Ferrone S, Marincola FM. Loss of HLA class I antigens by melanoma cells: molecular mechanisms, functional significance and clinical relevance. Immunol Today 1995; 16:487–494.
Restifo NP, et al. Identification of human cancers deficient in antigen processing. J Exp Med 1993; 177:265–272.
Seliger B, et al. Analysis of the major histocompatibility complex class I antigen presentation machinery in normal and malignant renal cells: evidence for deficiencies associated with transformation and progression. Cancer Res 1996; 56:1756–1760.
Johnsen AK, Templeton DJ, Sy M, Harding CV. Deficiency of transporter for antigen presentation (TAP) in tumor cells allows evasion of immune surveillance and increases tumorigenesis. J Immunol 1999; 163:4224–4231.
Townsend SE, Allison JP. Tumor rejection after direct costimulation of CD8+ T cells by B7-transfected melanoma cells. Science 1993; 259:368–370.
Chen L, et al. Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. Cell 1992; 71:1093–1102.
Restifo NP, et al. Molecular mechanisms used by tumors to escape immune recognition: immunogenetherapy and the cell biology of major histocompatibility complex class I. J Immunother 1993; 14:182–190.
Armstrong TD, et al. Major histocompatibility complex class II-transfected tumor cells present endogenous antigen and are potent inducers of tumor-specific immunity. Proc Natl Acad Sci USA 1997; 94:6886–6891.
Baskar S, et al. Constitutive expression of B7 restores immunogenicity of tumor cells expressing truncated major histocompatibility complex class II molecules. Proc Natl Acad Sci USA 1993; 90:5687–5690.
Fearon ER, et al. Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell 1990; 60:397–403.
Golumbek PT, et al. Treatment of established renal cancer by tumor cells engineered to secrete interleukin-4. Science 1991; 254:713–716.
Paglia P, Chiodoni C, Rodolfo M, Colombo MP. Murine dendritic cells loaded in vitro with soluble protein prime cytotoxic T lymphocytes against tumor antigen in vivo. J Exp Med 1996; 183:317–322.
Celluzzi CM, et al. Peptide-pulsed dendritic cells induce antigen-specific CTL-mediated protective tumor immunity. J Exp Med 1996; 183:283–287.
Nestle FO, et al. Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med 1998; 4:328–332.
Hsu FJ, et al. Vaccination of patients with B-cell lymphoma using autologous antigen-pulsed dendritic cells. Nat Med 1996; 2:52–58.
Smith SG. The polyepitope approach to DNA vaccination. Curr Opin Mol Ther 1999; 1:10–15.
Boczkowski D, Nair SK, Snyder D, Gilboa E. Dendritic cells pulsed with RNA are potent antigen-presenting cells in vitro and in vivo. J Exp Med 1996; 184:465–472.
Lambert L, Gibson G, Maloney M, Barth R. Equipotent generation of protective antitumor immunity by various methods of dendritic cell loading with whole cell tumor antigens. J Immunother 2001; 24:232–236.
Zheng L, et al. Delivery of liposome-encapsulated HIV type 1 proteins to human dendritic cells for stimulation of HIV type 1-specific memory cytotoxic T lymphocyte responses. AIDS Res Hum Retroviruses 1999; 15:1011–1020.
Wang J, et al. Eliciting T cell immunity against poorly immunogenic tumors by immunization with dendritic cell-tumor fusion vaccines. J Immunol 1998; 161:5516–5524.
Gong J, Chen D, Kashiwaba M, Kufe D. Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells. Nat Med 1997; 3:558–561.
Schuler G, Steinman RM. Dendritic cells as adjuvants for immune-mediated resistance to tumors. J Exp Med 1997; 186:1183–1187.
Banchereau J, et al. Immune and clinical responses in patients with metastatic melanoma to CD34(+) progenitor-derived dndritic cell vaccine. Cancer Res 2001; 61:6451–6458.
Guo Y, et al. Effective tumor vaccine generated by fusion of hepatoma cells with activated B cells. Science 1994; 263:518–520.
Galea-Lauri J, et al. Eliciting cytotoxic T lymphocytes against acute myeloid leukemia-derived antigens: evaluation of dendritic cell-leukemia cell hybrids and other antigen-loading strategies for dendritic cell-based vaccination. Cancer Immunol Immunother 2002; 51:299–310.
Kugler A, et al. Autologous and allogenic hybrid cell vacine in patients with metastatic renal cell carcinoma. Br J Urol 1998; 82:487–493.
Gong J, et al. Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and breast carcinoma cells. Proc Natl Acad Sci USA 2000; 97:2715–2718.
Kikuchi T, et al. Results of a phase I clinical trial of vaccination of glioma patients with fusions of dendritic and glioma cells. Cancer Immunol Immunother 2001; 50:337–344.
Soruri A, et al. Ex vivo generation of human anti-melanoma autologous cytolytic T cells by dentritic cell/melanoma cell hybridomas. Cancer Immunol Immunother 2001; 50:307–314.
Holmes LM, et al. A rapid, novel strategy to induce tumor cell-specific cytotoxic T lymphocyte responses using instant dentritomas. J Immunother 2001; 24:122–129.
Jonuleit H, et al. A comparison of two types of dendritic cell as adjuvants for the induction of melanoma-specific T-cell responses in humans following intranodal injection. Int J Cancer 2001; 93:243–251.
Oluwole SF, et al. Migration patterns of dendritic cells in the rat: comparison of the effects of gamma and UV-B irradiation on the migration of dendritic cells and Lymphocytes. Cell Immunol 1991; 133:390–407.
Bhardwaj N, Seder RA, Reddy A, Feldman MV. IL-12 in conjunction with dendritic cells enhances antiviral CD8+ CTL responses in vitro. J Clin Invest 1996; 98:715–722.
Jonuleit H, Schmitt E, Steinbrink K, Enk AH. Dendritic cells as a tool to induce anergic and regulatory T cells. Trends Immunol 2001; 22:394–400.
Lundqvist A, et al. Recombinant adenovirus vector activates and protects human monocyte-derived dendritic cells from apoptosis. Hum Gene Ther 2002; 13:1541–1549.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lundqvist, A., Palmborg, A., Bidla, G. et al. Allogeneic tumor-dendritic cell fusion vaccines for generation of broad prostate cancer T-cell responses. Med Oncol 21, 155–165 (2004). https://doi.org/10.1385/MO:21:2:155
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1385/MO:21:2:155