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 STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Journal of Cancer Research and Clinical Oncology
Published in: Journal of Cancer Research and Clinical Oncology 7/2005

01-07-2005 | Original Paper

Intratumoral injection of interferon-gamma gene-modified dendritic cells elicits potent antitumor effects: effective induction of tumor-specific CD8+ CTL response

Authors: Jianping Pan, Minghui Zhang, Jianli Wang, Qingqing Wang, Dajing Xia, Wenji Sun, Lihuang Zhang, Hai Yu, Xuetao Cao

Published in: Journal of Cancer Research and Clinical Oncology | Issue 7/2005

Login to get access

Abstract

Purpose

To examine the antitumor efficacy of intratumoral injection of interferon-gamma gene-modified dendritic cells (DC-IFN-γ) in a B16 melanoma model and to investigate its related immunological mechanisms.

Methods

C57BL/6 mice-derived DC were transfected with adenovirus encoding IFN-γ or β-galactosidase (DC-LacZ). Secretion of IFN-γ and TNF-α by DC was detected by ELISA. Nitric oxide (NO) production was measured by Griess reaction. Cytotoxicity of DC against tumor cell lines and activity of cytotoxic T lymphocytes (CTLs) were determined by 51Cr-release assay. TRP-2aa180–188-specific CD8+ CTLs in tumor-bearing mice with different treatment were determined by ELISPOT.

Results

DC-IFN-γ could secrete high levels of IFN-γ, NO and TNF-α. DC-IFN-γ were cytolytic to B16 melanoma cells in vitro, but DC-LacZ and DC were not. Significant inhibition of tumor growth and prolonged survival were achieved in tumor-bearing mice intratumorally injected with DC-IFN-γ when compared with those in tumor-bearing mice intratumorally injected with DC, DC-LacZ, fibroblasts, IFN-γ gene-modified fibroblasts or PBS. After treatment with DC-IFN-γ, enhanced Th1 and decreased Th2 responses were observed, and B16 melanoma antigen TRP-2aa180–188-specific CD8+ CTLs were induced significantly in the tumor-bearing mice.

Conclusions

Intratumorally injected DC-IFN-γ can uptake tumor antigens in situ and cross-present tumor antigens to specific CD8+ T cells, hereby eliciting effective antitumor effects in murine model with preestablished B16 melanoma.
Literature
Albert ML, Sauter B, Bhardwaj N (1998) Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392:86–89PubMedCrossRef
Bellone M, Iezzi G, Rovere P, Galati G, Ronchetti A, Protti MP, Davoust J, Rugarli C, Manfredi AA (1997) Processing of engulfed apoptotic bodies yields T cell epitopes. J Immunol 159:5391–5399PubMed
Bloom MB, Perry-Lalley D, Robbins PF, Li Y, el-Gamil M, Rosenberg SA, Yang JC (1997) Identification of tyrosinase-related protein 2 as a tumor rejection antigen for B16 melanoma. J Exp Med 185:453–459PubMedPubMedCentralCrossRef
Candido KA, Shimizu K, McLaughlin JC, Kunkel R, Fuller JA, Redman BG, Thomas EK, Nickoloff BJ, Mule JJ (2001) Local administration of dendritic cells inhibits established breast tumor growth: implications for apoptosis-inducing agents. Cancer Res 61:228–236PubMed
Cao X, Zhang W, He L, Xie Z, Ma S, Tao Q, Yu Y, Hamada H, Wang J (1998) Lymphotactin gene-modified bone marrow dendritic cells act as more potent adjuvants for peptide delivery to induce specific antitumor immunity. J Immunol 161:6238–6244PubMed
Cordier Kellerman L, Valeyrie L, Fernandez N, Opolon P, Sabourin JC, Maubec E, Roy PL, Kane A, Legrand A, Abina MA, Descamps V, Haddada H (2003) Regression of AK7 malignant mesothelioma established in immunocompetent mice following intratumoral gene transfer of interferon gamma. Cancer Gene Ther 10:481–490CrossRef
Dietrich A, Kraus K, Brinckmann U, Stockmar C, Muller A, Liebert UG, Schonfelder M (2003) Antitumoral and antimetastatic effects of continuous particle-mediated cytokine gene therapy. Recent Results Cancer Res 162:157–168PubMedCrossRef
Fields RC, Shimizu K, Mulle JJ (1998) Murine dendritic cells pulsed with whole tumor lysates mediate potent antitumor immune responses in vitro and in vivo. Proc Natl Acad Sci USA 95:9482–9487PubMedPubMedCentralCrossRef
Frucht DM, Fukao T, Bogdan C, Schindler H, O’Shea JJ, Koyasu S (2001) IFN-gamma production by antigen-presenting cells: mechanisms emerge. Trends Immunol 22:556–560PubMedCrossRef
Gattacceca F, Pilatte Y, Billard C, Monnet I, Moritz S, Le Carrou J, Eloit M, Jaurand MC (2002) Ad-IFN gamma induces antiproliferative and antitumoral responses in malignant mesothelioma. Clin Cancer Res 8:3298–3304PubMed
Geiger JD, Hutchinson RJ, Hohenkirk LF, McKenna EA, Yanik GA, Levine JE, Chang AE, Braun TM, Mule JJ (2001) Vaccination of pediatric solid tumor patients with tumor lysate-pulsed dendritic cells can expand specific T cells and mediate tumor regression. Cancer Res 61:8513–8519PubMed
Hoffmann TK, Meidenbauer N, Dworacki G, Kanaya H, Whiteside TL (2000) Generation of tumor-specific T-lymphocytes by cross-priming with human dendritic cells ingesting apoptotic tumor cells. Cancer Res 60:3542–3549PubMed
Janjic BM, Lu G, Pimenov A, Whiteside TL, Storkus WJ, Vujanovic NL (2002) Innate direct anticancer effector function of human immature dendritic cells. I. Involvement of an apoptosis-inducing pathway. J Immunol 168:1823–1830PubMedCrossRef
Jenne L, Arrighi JF, Jonuleit H, Saurat JH, Hauser C (2000) Dendritic cells containing apoptotic melanoma cells prime human CD8+ T cells for efficient tumor cell lysis. Cancer Res 60:4446–4452PubMed
Kirk CJ, Mule JJ (2000) Gene-modified dendritic cells for use in tumor vaccines. Hum Gene Ther 11:797–806PubMedCrossRef
Kotera Y, Shimizu K, JJ Mule (2001) Comparative analysis of necrotic and apoptotic tumor cells as a source of antigen(s) in dendritic cell-based immunization. Cancer Res 61:8105–8109PubMed
Labarriere N, Bretaudeau L, Gervois N, Bodinier M, Bougras G, Diez E, Lang F, Gregoire M, Jotereau F (2002) Apoptotic body-loaded dendritic cells efficiently cross-prime cytotoxic T lymphocytes specific for NA17-A antigen but not for Melan-A/MART-1 antigen. Int J Cancer 101:280–286PubMedCrossRef
Langaas V, Shahzidi S, Johnsen JI, Smedsrod B, Sveinbjornsson B (2001) Interferon-gamma modulates TRAIL-mediated apoptosis in human colon carcinoma cells. Anticancer Res 21:3733–3788PubMed
Lei H, Ju DW, Yu Y, Tao Q, Chen G, Gu S, Hamada H, Cao X (2000) Induction of potent antitumor response by vaccination with tumor lysate-pulsed macrophages engineered to secrete macrophage colony-stimulating factor and interferon-gamma. Gene Ther 7:707–713PubMedCrossRef
Liu S, Yu Y, Zhang M, Wang W, Cao X (2001) The involvement of TNF-alpha-related apoptosis-inducing ligand in the enhanced cytotoxicity of IFN-beta-stimulated human dendritic cells to tumor cells. J Immunol 166:5407–5415PubMedCrossRef
Lu G, Janjic BM, Janjic J, Whiteside TL, Storkus WJ, Vujanovic NL (2002) Innate direct anticancer effector function of human immature dendritic cells. II. Role of TNF, lymphotoxin-alpha(1)beta(2), Fas ligand, and TNF-related apoptosis- inducing ligand. J Immunol 168:1831–1839PubMedCrossRef
Masse D, Voisine C, Henry F, Cordel S, Barbieux I, Josien R, Meflah K, Gregoire M, Lieubeau B (2002) Increased vaccination efficiency with apoptotic cells by silica-induced, dendritic-like cells. Cancer Res 62:1050–1056PubMed
Mellman I, Steinman RM (2001) Dendritic cells: specialized and regulated antigen processing machines. Cell 106:255–258PubMedCrossRef
Miller PW, Sharma S, Stolina M, Butterfield LH, Luo J, Lin Y, Dohadwala M, Batra RK, Wu L, Economou JS, Dubinett SM (2000) Intratumoral administration of adenoviral interleukin 7 gene-modified dendritic cells augments specific antitumor immunity and achieves tumor eradication. Hum Gene Ther 11:53–65PubMedCrossRef
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 4:328–332PubMedCrossRef
Paczesny S, Beranger S, Salzmann JL, Klatzmann D, Colombo BM (2001) Protection of mice against leukemia after vaccination with bone marrow-derived dendritic cells loaded with apoptotic leukemia cells. Cancer Res 61:2386–2389PubMed
Pan J, Ju D, Wang Q, Zhang M, Xia D, Zhang L, Yu H, Cao X (2001) Dexamethasone inhibits the antigen presentation of dendritic cells in MHC class II pathway. Immunol Lett 76:153–161PubMedCrossRef
Pan J, Zhang M, Wang J, Wang Q, Xia D, Sun W, Zhang L, Yu H, Liu Y, Cao X (2004) Interferon-γ is an autocrine mediator for dendritic cell maturation. Immunol Lett 94:141–151PubMedCrossRef
Park SY, Billiar TR, Seol DW (2002) IFN-gamma inhibition of TRAIL-induced IAP-2 upregulation, a possible mechanism of IFN-gamma-enhanced TRAIL-induced apoptosis. Biochem Biophys Res Commun 291:233–236PubMedCrossRef
Ribas A, Butterfield LH, Glaspy JA, Economou JS (2002) Cancer immunotherapy using gene-modified dendritic cells. Curr Gene Ther 2:57–78PubMedCrossRef
Ruuls SR, Hoek RM, Ngo VN, McNeil T, Lucian LA, Janatpour MJ, Korner H, Scheerens H, Hessel EM, Cyster JG, McEvoy LM, Sedgwick JD (2001) Membrane-bound TNF supports secondary lymphoid organ structure but is subservient to secreted TNF in driving autoimmune inflammation. Immunity 15:533–543PubMedCrossRef
Sasagawa T, Hlaing M, Akaike T (2000) Synergistic induction of apoptosis in murine hepatoma Hepa1–6 cells by IFN-gamma and TNF-alpha. Biochem Biophys Res Commun 272:674–680PubMedCrossRef
Shaif-Muthana M, McIntyre C, Sisley K, Rennie I, Murray A (2000) Dead or alive: immunogenicity of human melanoma cells when presented by dendritic cells. Cancer Res 60:6441–6447PubMed
Shimamura H, Cumberland R, Hiroishi K, Watkins SC, Lotze MT, Baar J (2002) Murine dendritic cell-induced tumor apoptosis is partially mediated by nitric oxide. J Immunother 25:226–234PubMedCrossRef
Shin EC, Ahn JM, Kim CH, Choi Y, Ahn YS, Kim H, Kim SJ, Park JH (2001) IFN-gamma induces cell death in human hepatoma cells through a TRAIL/death receptor-mediated apoptotic pathway. Int J Cancer 93:262–268PubMedCrossRef
Steitz J, Bruck J, Knop J, Tuting T (2001) Adenovirus-transduced dendritic cells stimulate cellular immunity to melanoma via a CD4(+) T cell-dependent mechanism. Gene Ther 8:1255–1263PubMedCrossRef
Tanaka F, Yamaguchi H, Ohta M, Mashino K, Sonoda H, Sadanaga N, Inoue H, Mori M (2002) Intratumoral injection of dendritic cells after treatment of anticancer drugs induces tumor-specific antitumor effect in vivo. Int J Cancer 101:265–269PubMedCrossRef
Toes RE, van der Voort EI, Schoenberger SP, Drijfhout JW, van Bloois L, Storm G, Kast WM, Offringa R, Melief CJ (1998) Enhancement of tumor outgrowth through CTL tolerization after peptide vaccination is avoided by peptide presentation on dendritic cells. J Immunol 160:4449–4456PubMed
Varela N, Munoz-Pinedo C, Ruiz-Ruiz C, Robledo G, Pedroso M, Lopez-Rivas A (2001) Interferon-gamma sensitizes human myeloid leukemia cells to death receptor-mediated apoptosis by a pleiotropic mechanism. J Biol Chem 276:17779–17787PubMedCrossRef
Walczak H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M, Chin W, Jones J, Woodward A, Le T, Smith C, Smolak P, Goodwin RG, Rauch CT, Schuh JC, Lynch DH (1999) Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat Med 5:157–163PubMedCrossRef
Zhang W, He L, Yuan Z, Wang J, Hamada H, Cao X (1999) Enhanced therapeutic efficacy of tumor RNA-pulsed dendritic cells after genetic modification with lymphotactin. Hum Gene Ther 10:1151–1161PubMedCrossRef
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 183:87–97PubMedCrossRef
Metadata
Title
Intratumoral injection of interferon-gamma gene-modified dendritic cells elicits potent antitumor effects: effective induction of tumor-specific CD8+ CTL response
Authors
Jianping Pan
Minghui Zhang
Jianli Wang
Qingqing Wang
Dajing Xia
Wenji Sun
Lihuang Zhang
Hai Yu
Xuetao Cao
Publication date
01-07-2005
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 7/2005
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-004-0651-y

Other articles of this Issue 7/2005

Journal of Cancer Research and Clinical Oncology 7/2005 Go to the issue

Original Paper

Prognostic value of cyclin D1 overexpression in correlation with pRb and p53 status in non-small cell lung cancer (NSCLC)

Original Paper

The biological effect of pentoxifylline on the survival of human head and neck cancer cells treated with continuous low and high dose-rate irradiation

Review

70 Gy or more: which dose for which prostate cancer?

Original Paper

Polymorphism in the manganese superoxide dismutase (MnSOD) gene and risk of breast cancer in young women

Original Paper

Macrophage level is not affected by monocyte chemotactic protein-1 in invasive ductal breast carcinoma

Original Paper

Induction of tumor immunity and cytotoxic t lymphocyte responses using dendritic cells transduced by adenoviral vectors encoding HBsAg: comparison to protein immunization
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits