Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 8/2004

01-08-2004 | Original Article

Antitumor effects of fusions composed of dendritic cells and fibroblasts transfected with genomic DNA from tumor cells

Authors: Motoyuki Nakamura, Tetsuro Kikuchi, Donald W. Kufe, Tsuneya Ohno

Published in: Cancer Immunology, Immunotherapy | Issue 8/2004

Login to get access

Abstract

Based on several previous studies indicating that transfection of genomic DNA can stably alter the character of the cells that take up the exogenous DNA, we investigated antitumor immunity conferred by fusions of syngeneic dendritic cells (DCs) and allogeneic fibroblasts (NIH3T3) transfected with genomic DNA from B16 tumor cells. Fusion cells (FCs) composed of dendritic and genetically engineered NIH3T3 cells were prepared with polyethylene glycol, and fusion efficiency was 30.3%. Prior immunization with FCs prevented tumor formation upon challenge with B16 tumor cells. Efficacy was reduced when studies were performed in mice depleted of NK cells. Vaccination with FCs containing DCs and fibroblasts transfected with denatured DNA did not inhibit tumor growth. Cytotoxic T cell (CTL) activity of spleen cells from immunized mice against both Yac-1 and tumor cells was also stimulated by administration of FCs compared with the activity observed for cells obtained from naïve mice. These data demonstrate the therapeutic efficacy of fusion cell–based vaccine therapy using syngeneic DCs and allogeneic fibroblasts transfected with tumor-derived genomic DNA.
Literature
1.
Steinman RM (1991) The dendritic cell system and its role in immunogenicity. Annu Rev Immunol 9:271PubMed
2.
Nestle FO, Alijagic S, Gilliet M, Sun Y, Grabbe S, Dummer R, Burg G, Schadendorf D (1998) Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells. Nat Med 4:328PubMed
3.
Reeves ME, Royal RE, Lam JS, Rosenberg SA, Hwu P (1996) Retroviral transduction of human dendritic cells with a tumor- associated antigen gene. Cancer Res 56:5672PubMed
4.
Zitvogel L, Mayordomo JI, Tjandrawan T, DeLeo AB, Clarke MR, Lotze MT, Storkus WJ (1996) Therapy of murine tumors with tumor peptide-pulsed dendritic cells: dependence on T cells, B7 costimulation, and T helper cell 1-associated cytokines. J Exp Med 183:87PubMed
5.
Tuting T, Wilson CC, Martin DM, Kasamon YL, Rowles J, Ma DI, Slingluff CL, Wagner SN, van der Bruggen P, Baar J, Lotze MT, Storkus WJ (1998) Autologous human monocyte-derived dendritic cells genetically modified to express melanoma antigens elicit primary cytotoxic T cell responses in vitro: enhancement by cotransfection of genes encoding the Th1- biasing cytokines IL-12 and IFN-alpha. J Immunol 160:1139PubMed
6.
Celluzzi CM, Falo LD (1998) Physical interaction between dendritic cells and tumor cells results in an immunogen that induces protective and therapeutic tumor rejection. J Immunol 160:3081PubMed
7.
Akasaki Y, Kikuchi T, Homma S, Abe T, Kufe D, Ohno T (2001) Antitumor effect of immunizations with fusions of dendritic and glioma cells in a mouse brain tumor model. J Immunother 24:106
8.
Gong J, Chen D, Kashiwaba M, Kufe D (1997) Induction of antitumor activity by immunization with fusions of dendritic and carcinoma cells. Nat Med 3:558PubMed
9.
Gong J, Chen D, Kashiwaba M, Li Y, Chen L, Takeuchi H, Qu H, Rowse GJ, Gendler SJ, Kufe D (1998) Reversal of tolerance to human MUC1 antigen in MUC1 transgenic mice immunized with fusions of dendritic and carcinoma cells. Proc Natl Acad Sci U S A 95:6279CrossRefPubMed
10.
Wigler M, Pellicer A, Silverstein S, Axel R (1978) Biochemical transfer of single-copy eucaryotic genes using total cellular DNA as donor. Cell 14:725PubMed
11.
de Zoeten E, Carr-Brendel V, Markovic D, Taylor-Papadimitriou J, Cohen EP (1999) Treatment of breast cancer with fibroblasts transfected with DNA from breast cancer cells. J Immunol 162:6934PubMed
12.
Whiteside TL, Gambotto A, Albers A, Stanson J, Cohen EP (2002) Human tumor-derived genomic DNA transduced into a recipient cell induces tumor-specific immune responses ex vivo. Proc Natl Acad Sci U S A 99:9415CrossRefPubMed
13.
Ecsedy JA, Manfredi MG, Yohe HC, Seyfried TN (1997) Ganglioside biosynthetic gene expression in experimental mouse brain tumors. Cancer Res 57:1580PubMed
14.
Housey GM, Johnson MD, Hsiao WL, O’Brian CA, Murphy JP, Kirschmeier P, Weinstein IB (1988) Overproduction of protein kinase C causes disordered growth control in rat fibroblasts. Cell 52:343PubMed
15.
Yoshimatsu T, Tamura M, Kuriyama S, Ikenaka K (1998) Improvement of retroviral packaging cell lines by introducing the polyomavirus early region. Hum Gene Ther 9:161PubMed
16.
Kikuchi T, Joki T, Saitoh S, Hata Y, Abe T, Kato N, Kobayashi A, Miyazaki T, Ohno T (1999) Anti-tumor activity of interleukin-2-producing tumor cells and recombinant interleukin 12 against mouse glioma cells located in the central nervous system. Int J Cancer 80:425PubMed
17.
Ribas A, Bui LA, Butterfield LH, Vollmer CM, Jilani SM, Dissette VB, Glaspy JA, McBride WH, Economou JS (1999) Antitumor protection using murine dendritic cells pulsed with acid-eluted peptides from in vivo grown tumors of different immunogenicities. Anticancer Res 19:1165PubMed
18.
Kaneko K, Wang Z, Kim SH, Morelli AE, Robbins PD, Thomson AW (2003) Dendritic cells genetically engineered to express IL-4 exhibit enhanced IL-12p70 production in response to CD40 ligation and accelerate organ allograft rejection. Gene Ther 10:143CrossRefPubMed
19.
Nakamura M, Iwahashi M, Nakamori M, Ueda K, Matsuura I, Noguchi K, Yamaue H (2002) Dendritic cells genetically engineered to simultaneously express endogenous tumor antigen and granulocyte macrophage colony-stimulating factor elicit potent therapeutic antitumor immunity. Clin Cancer Res 8:2742PubMed
20.
Nelson WG, Simons JW, Mikhak B, Chang JF, DeMarzo AM, Carducci MA, Kim M, Weber CE, Baccala AA, Goeman MA, Clift SM, Ando DG, Levitsky HI, Cohen LK, Sanda MG, Mulligan RC, Partin AW, Carter HB, Piantadosi S, Marshall FF (2000) Cancer cells engineered to secrete granulocyte-macrophage colony-stimulating factor using ex vivo gene transfer as vaccines for the treatment of genitourinary malignancies. Cancer Chemother Pharmacol 46[Suppl]:S67
21.
Schoenberger SP, Jonges LE, Mooijaart RJ, Hartgers F, Toes RE, Kast WM, Melief CJ, Offringa R (1998) Efficient direct priming of tumor-specific cytotoxic T lymphocyte in vivo by an engineered APC. Cancer Res 58:3094PubMed
22.
Joki T, Kikuchi T, Akasaki Y, Saitoh S, Abe T, Ohno T (1999) Induction of effective antitumor immunity in a mouse brain tumor model using B7-1 (CD80) and intercellular adhesive molecule 1 (ICAM-1; CD54) transfection and recombinant interleukin 12. Int J Cancer 82:714CrossRefPubMed
23.
Yu Y, Hagihara M, Ando K, Gansuvd B, Matsuzawa H, Tsuchiya T, Ueda Y, Inoue H, Hotta T, Kato S (2001) Enhancement of Human Cord Blood CD34(+) Cell-Derived NK Cell Cytotoxicity by Dendritic Cells. J Immunol 166:1590PubMed
Metadata
Title
Antitumor effects of fusions composed of dendritic cells and fibroblasts transfected with genomic DNA from tumor cells
Authors
Motoyuki Nakamura
Tetsuro Kikuchi
Donald W. Kufe
Tsuneya Ohno
Publication date
01-08-2004
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 8/2004
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-004-0511-2

Other articles of this Issue 8/2004

Cancer Immunology, Immunotherapy 8/2004 Go to the issue

Original Article

An epigenetically altered tumor cell vaccine

Original Article

CpG-Oligodeoxynucleotides activate tyrosinase-related protein 2–specific T lymphocytes but do not lead to a protective tumor-specific memory response

Meeting Report

Strategies for immune therapy: Würzburg, Germany, 29 February–3 March 2004

Original Article

Anandamide is an endogenous inhibitor for the migration of tumor cells and T lymphocytes

Review

Immunotherapy of cancer for the elderly patient: does allogeneic bone marrow transplantation after nonmyeloablative conditioning provide a new option?

Opinion Paper

How should clinical data be included in experimental studies of cancer immunology?
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits