scholarly journals Comparative Analysis of Genetically Modified Dendritic Cells and Tumor Cells as Therapeutic Cancer Vaccines

2000 ◽  
Vol 191 (10) ◽  
pp. 1699-1708 ◽  
Author(s):  
Christoph Klein ◽  
Hansruedi Bueler ◽  
Richard C. Mulligan
Keyword(s):  
Dendritic Cells ◽  
Gene Transfer ◽  
Tumor Cells ◽  
Therapeutic Effect ◽  
Genetically Modified ◽  
Tumor Model ◽  
Immunological Mechanism ◽  
Subcutaneous Tumor ◽  
Gm Csf ◽  
Metastasis Model

We have directly compared the efficacy of two immunotherapeutic strategies for the treatment of cancer: “vaccination” of tumor-bearing mice with genetically modified dendritic cells (DCs), and vaccination with genetically modified tumor cells. Using several different preexisting tumor models that make use of B16F10 melanoma cells expressing a target tumor antigen (human melanoma-associated gene [MAGE]-1), we found that vaccination with bone marrow–derived DCs engineered to express MAGE-1 via adenoviral-mediated gene transfer led to a dramatic decrease in the number of metastases in a lung metastasis model, and led to prolonged survival and some long-term cures in a subcutaneous preexisting tumor model. In contrast, vaccination with granulocyte/macrophage colony-stimulating factor (GM-CSF)–transduced tumor cells, previously shown to induce potent antitumor immunity in standard tumor challenge assays, led to a decreased therapeutic effect in the metastasis model and no effect in the subcutaneous tumor model. Further engineering of DCs to express either GM-CSF, tumor necrosis factor α, or CD40 ligand via retroviral-mediated gene transfer, led to a significantly increased therapeutic effect in the subcutaneous tumor model. The immunological mechanism, as shown for GM-CSF–transduced DCs, involves MAGE-1–specific CD4+ and CD8+ T cells. Expression of GM-CSF by DCs led to enhanced cytotoxic T lymphocyte activity, potentially mediated by increased numbers of DCs in draining lymph nodes. Our results suggest that clinical studies involving the vaccination with genetically modified DCs may be warranted.

Monoclonal antibody 2C5-mediated binding of liposomes to brain tumor cells in vitro and in subcutaneous tumor model in vivo

2005 ◽  
Vol 13 (6) ◽  
pp. 337-343 ◽  
Author(s):  
Bhawna Gupta ◽  
Tatiana S. Levchenko ◽  
Dmitry A. Mongayt ◽  
Vladimir P. Torchilin
Keyword(s):  
Monoclonal Antibody ◽  
Brain Tumor ◽  
Tumor Cells ◽  
Tumor Model ◽  
Subcutaneous Tumor ◽  
Brain Tumor Cells

Vaccination With Irradiated, Autologous Melanoma Cells Engineered to Secrete Granulocyte-Macrophage Colony-Stimulating Factor by Adenoviral-Mediated Gene Transfer Augments Antitumor Immunity in Patients With Metastatic Melanoma

2003 ◽  
Vol 21 (17) ◽  
pp. 3343-3350 ◽  
Author(s):  
Robert Soiffer ◽  
F. Stephen Hodi ◽  
Frank Haluska ◽  
Ken Jung ◽  
Silke Gillessen ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Metastatic Melanoma ◽  
Tumor Cells ◽  
Antitumor Immunity ◽  
Melanoma Cells ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Purpose: Vaccination with irradiated, autologous melanoma cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) by retroviral-mediated gene transfer generates potent antitumor immunity in patients with metastatic melanoma. Further clinical development of this immunization scheme requires simplification of vaccine manufacture. We conducted a phase I clinical trial testing the biologic activity of vaccination with irradiated, autologous melanoma cells engineered to secrete GM-CSF by adenoviral-mediated gene transfer.Patients and Methods: Excised metastases were processed to single cells, transduced with a replication-defective adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines were composed of 1 × 106, 4 × 106, or 1 × 107tumor cells, depending on overall yield, and were injected intradermally and subcutaneously at weekly and biweekly intervals.Results: Vaccines were successfully manufactured for 34 (97%) of 35 patients. The average GM-CSF secretion was 745 ng/106cells/24 hours. Toxicities were restricted to grade 1 to 2 local skin reactions. Eight patients were withdrawn early because of rapid disease progression. Vaccination elicited dense dendritic cell, macrophage, granulocyte, and lymphocyte infiltrates at injection sites in 19 of 26 assessable patients. Immunization stimulated the development of delayed-type hypersensitivity reactions to irradiated, dissociated, autologous, nontransduced tumor cells in 17 of 25 patients. Metastatic lesions that were resected after vaccination showed brisk or focal T-lymphocyte and plasma cell infiltrates with tumor necrosis in 10 of 16 patients. One complete, one partial, and one mixed response were noted. Ten patients (29%) are alive, with a minimum follow-up of 36 months; four of these patients have no evidence of disease.Conclusion: Vaccination with irradiated, autologous melanoma cells engineered to secrete GM-CSF by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma.

Phase I/II Trial of Melanoma Patient–Specific Vaccine of Proliferating Autologous Tumor Cells, Dendritic Cells, and GM-CSF: Planned Interim Analysis

2004 ◽  
Vol 19 (5) ◽  
pp. 658-665 ◽  
Author(s):  
Robert Dillman ◽  
Senthamil Selvan ◽  
Patric Schiltz ◽  
Cheryl Peterson ◽  
Kanoe Allen ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Phase I ◽  
Tumor Cells ◽  
Melanoma Patient ◽  
Interim Analysis ◽  
Patient Specific ◽  
Autologous Tumor ◽  
Gm Csf

scholarly journals Viral IL-10 Gene Transfer Inhibits DTH Responses to Soluble Antigens: Evidence for Involvement of Genetically Modified Dendritic Cells and Macrophages

2001 ◽  
Vol 4 (6) ◽  
pp. 543-550 ◽  
Author(s):  
Janey D. Whalen ◽  
Angus W. Thomson ◽  
Lina Lu ◽  
Paul D. Robbins ◽  
Christopher H. Evans
Keyword(s):  
Dendritic Cells ◽  
Gene Transfer ◽  
Genetically Modified

scholarly journals Bead-Selected Antitumor Genetic Cell Vaccines

2008 ◽  
Vol 2 ◽  
pp. CMO.S586
Author(s):  
Herrero Mj ◽  
R Botella ◽  
R Algás ◽  
FM Marco ◽  
Aliño Sf
Keyword(s):  
Gene Therapy ◽  
Immune Response ◽  
Tumor Cells ◽  
Murine Model ◽  
Cancer Vaccines ◽  
Genetically Modified ◽  
Cell Number ◽  
Gm Csf ◽  
Clinical Reality

Cancer vaccines have always been in the scope of gene therapy research. One of the most successful approaches has been working with genetically modified tumor cells. However, to become a clinical reality, tumor cells must suffer a long and risky process from the extraction from the patient to the reimplantation as a vaccine. In this work, we explain our group's approach to reduce the cell number required to achieve an immune response against a melanoma murine model, employing bead-selected B16 tumor cells expressing GM-CSF and B7.2.

Activated Dendritic Cells From Bone Marrow Cells of Mice Receiving Cytokine-Expressing Tumor Cells Are Associated With the Enhanced Survival of Mice Bearing Syngeneic Tumors

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4328-4335
Author(s):  
Shin-ichiro Fujii ◽  
Hirofumi Hamada ◽  
Koji Fujimoto ◽  
Taizo Shimomura ◽  
Makoto Kawakita
Keyword(s):  
Bone Marrow ◽  
T Cells ◽  
Dendritic Cells ◽  
Tumor Cells ◽  
Mononuclear Cells ◽  
Bone Marrow Cells ◽  
Interleukin 4 ◽  
Gm Csf ◽  
Tumor Bearing ◽  
Macrophage Colony

Dendritic cells (DCs), which phagocytose antigens and subsequently proliferate and migrate, may be the most powerful antigen-presenting cells that activate naive T cells. To determine their role in the immune response to tumors, we used WEHI-3B murine leukemia cells transduced with adenovirus vectors expressing cytokines. We found that mixtures of irradiated cells expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) plus those expressing interleukin-4 (IL-4) or tumor necrosis factor  (TNF) protected mice against WEHI-3B–induced leukemias. When bone marrow mononuclear cells (BMMNCs) obtained from mice that had been injected with irradiated, cytokine-expressing tumor cells were injected into tumor-bearing mice, the survival of the latter was significantly prolonged; the longest survival was observed in mice receiving BMMNCs containing an increased number of DCs from animals injected with a mixture of tumor cells expressing GM-CSF with those expressing IL-4. Assay for antileukemic effects in spleen of the latter animals showed specific antitumor cytotoxicity against WEHI-3B, suggesting that DCs from donor mice activate specific T cells in the tumor-bearing recipients. These results suggest that the infusion of syngeneic BMMNCs stimulated with cytokine-expressing tumor cells may be effective in treating certain types of tumors.

Synergy Between Dendritic Cells and GM–CSF-secreting Tumor Cells for the Treatment of a Murine Renal Cell Carcinoma

2009 ◽  
Vol 32 (2) ◽  
pp. 140-144 ◽  
Author(s):  
Gregory Driessens ◽  
Paul Hoffmann ◽  
Michael Pouwels ◽  
Alexandre Zlotta ◽  
Claude Schulman ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Dendritic Cells ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Renal Cell ◽  
Gm Csf

scholarly journals Gene transfer of CD40-ligand to dendritic cells stimulates interferon-γ production to induce growth arrest and apoptosis of tumor cells

Gene Therapy ◽  
2007 ◽  
Vol 15 (3) ◽  
pp. 203-213 ◽  
Author(s):  
K Tomihara ◽  
K Kato ◽  
Y Masuta ◽  
K Nakamura ◽  
H Uchida ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Gene Transfer ◽  
Tumor Cells ◽  
Growth Arrest ◽  
Cd40 Ligand ◽  
Interferon Γ ◽  
Induce Growth Arrest
Sign in / Sign up

Export Citation Format

Share Document