Biomedical subjects

Masaki Nakamura

Publications and source records attributed to Masaki Nakamura.

At least 19 recordsLinked to original sources

PubMed2007

Successful cancer vaccine therapy for carcinoembryonic antigen (CEA)-expressing colon cancer using genetically modified dendritic cells that express CEA and T helper-type 1 cytokines in CEA transgenic mice.

This study was designed to determine whether the vaccination of genetically modified dendritic cells (DCs) simultaneously expressing carcinoembryonic antigen (CEA), granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin 12 (IL-12) can overcome the peripheral T-cell tolerance to CEA and thereby elicit a therapeutic response in CEA transgenic mice. CEA transgenic mice were immunized once by subcutaneous injection with DCs adenovirally transduced with CEA and T helper-type 1 cytokine genes. The cytotoxic activity of spleen cells against CEA-expressing tumors, MC38-CEA, in the mice immunized with DCs expressing CEA (DC-AxCACEA) was higher than that in those immunized with DCs-AxCALacZ (p < 0.0001), and was augmented by the cotransduction with the GM-CSF/IL-12 gene (p < 0.05). The vaccination with DC-AxCACEA/GM-CSF/IL-12 could elicit a more potent therapeutic immunity than the vaccination with DC-AxCACEA in subcutaneous tumor models (p < 0.0001), and 4 of 5 mice showed a complete eradication of the subcutaneous tumors in these vaccination groups. Even in a large tumor model, this vaccination therapy completely eliminated the subcutaneous tumors in all mice. This antitumor activity mostly vanished with the depletion of CD8(+) T cells and NK cells in vivo and was completely abrogated with the depletion of CD4(+) T cells. A histopathological examination showed no evidence of an autoimmune reaction. No other adverse effects were observed. This vaccination strategy resulted in the generation of highly efficient therapeutic immune responses against MC38-CEA in the absence of autoimmune responses and demonstrated no adverse effects, and may therefore be useful for future clinical applications as a cancer vaccine therapy.

Animals↗

PubMed2006

Negative regulation of osteoclastogenesis by ectodomain shedding of receptor activator of NF-kappaB ligand.

Receptor activator of NF-kappaB ligand (RANKL) is a transmembrane glycoprotein that has an essential role in the development of osteoclasts. The extracellular portion of RANKL is cleaved proteolytically to produce soluble RANKL, but definite RANKL sheddase(s) and the physiologic function of RANKL shedding have not yet been determined. In the present study, we found that matrix metalloproteinase (MMP) 14 and a disintegrin and metalloproteinase (ADAM) 10 have strong RANKL shedding activity. In Western blot analysis, soluble RANKL was detected as two different molecular weight products, and RNA interference of MMP14 and ADAM10 resulted in a reduction of both the lower and higher molecular weight products. Suppression of MMP14 in primary osteoblasts increased membrane-bound RANKL and promoted osteoclastogenesis in cocultures with macrophages. Soluble RANKL produced by osteoblasts from MMP14-deficient mice was markedly reduced, and their osteoclastogenic activity was promoted, consistent with the findings of increased osteoclastogenesis in vivo. RANKL shedding is an important process that down-regulates local osteoclastogenesis.

ADAM Proteins↗

PubMed2006

Surgical management of small gastrointestinal stromal tumors of the stomach.

Small gastrointestinal stromal tumors (GISTs) (< 3 cm) occasionally are found in the stomach during endoscopy. There is no consensus about the surgical management of these small tumors, although this clinical issue is crucial because some of the tumors show unexpected malignant behavior. In this study, we evaluated the clinical management of patients with gastric GISTs who underwent surgical resection. Altogether, 31 patients with gastric GISTs were examined retrospectively. Surgical resection was fundamentally indicated for the patients with gastric GISTs suspected to be malignant by endoscopy or endoscopic ultrasonography (EUS). The malignant grade of the GISTs was evaluated by the mitotic rate, tumor size, and MIB-1 index. EUS was useful for differentiating benign from malignant GISTs; but by limiting the study to patients with small tumors (< 3 cm), the diagnostic value of EUS was not satisfactory for defining the surgical indication. Tumors that were < 50 mm were successfully treated by laparoscopic surgery. Of the 31 patients, 4 had a relapse of the disease, and 1 of those 4 patients had a small tumor (30 mm). All of the recurrences were classified in the high risk category. Surgery is indicated for gastric GISTs that are > or = 20 mm or are suspected to be malignant based on EUS findings. Laparoscopic resection is feasible and is recommended as the treatment of choice for patients with tumors < 50 mm. Risk assessment can be most useful for predicting recurrence.

Aged↗

PubMed2006

Detection of Streptococcus species by polymerase chain reaction in infectious crystalline keratopathy.

PURPOSE: Investigation of a positive polymerase chain reaction (PCR) for Streptococcus species from an excised cornea of a patient with infectious crystalline keratopathy. METHODS: Samples microdissected from corneal intrastromal aggregates present in infectious crystalline keratopathy were subjected to PCR for 3 primer pairs respectively specific for Streptococcus, Staphylococcus, and several kinds of fungi. RESULTS: The PCR detected DNA from Streptococcus but not from Staphylococcus or fungi. Direct sequencing of the PCR products showed that the PCR products had the highest identity (99.8%) with Streptococcus mitis and Streptococcus gordoni, indicating that these species were the most probable causes of infectious crystalline keratopathy in this patient. CONCLUSION: Our findings suggest that PCR provides a good adjunct technique in the diagnosis of corneal infection.

Aged↗

PubMed2006

Molecular mechanism of the life and death of the osteoclast.

The life span of osteoclasts is critically regulated by various cytokines, and therapeutics such as bisphosphonates act directly on osteoclasts and induce apoptosis of the cells. This article will focus on the molecular mechanism of osteoclast apoptosis and summarize the recent advances in this field with an emphasis on the role of intracellular signaling pathways.

Animals↗

PubMed2006

The boosting effect of co-transduction with cytokine genes on cancer vaccine therapy using genetically modified dendritic cells expressing tumor-associated antigen.

The T-helper 1 (Th1) immune reaction is most important in dendritic cell (DC)-based immunotherapy. Interleukin 12 (IL-12) and granulocyte macrophage colony-stimulating factor (GM-CSF) play a pivotal role in inducing Th1 and cytotoxic T lymphocyte (CTL) responses. In this study, DCs expressing the natural tumor antigen gp70 of BALB/c-derived CT26 were adenovirally transduced with the IL-12 gene and/or GM-CSF gene, and it was examined whether vaccinations using these genetically engineered DCs can induce strong therapeutic antitumor immunity. Mice were immunized once by subcutaneous (s.c.) injection with genetically modified DCs. The cytotoxic activity of splenocytes against CT26 was assayed in a 51Cr-release assay 14 days after immunization. The therapeutic efficacy of the vaccination was examined in s.c. tumor models. The cytotoxic activity of CTLs against CT26 in mice immunized with DCs expressing gp70 (DC-AxCAgp70) was significantly augmented by co-transduction with the GM-CSF/IL-12 gene (p<0.0001) and remarkably reduced by the depletion of CD4+ or CD8+ cells (p<0.01). The cytotoxic activity against CT26 of the plain spleen cells in mice immunized with DC-AxCAgp70/GM-CSF/IL-12 was significantly higher than that in mice immunized with DC-AxCAgp70 (p<0.0001), and this activity decreased to almost 50% upon the depletion of NK cells. Vaccinations using DC-AxCAgp70/GM-CSF/IL-12 or DC-AxCAgp70/IL-12 could elicit potent therapeutic immunity in s.c. tumor models; tumor-free mice were observed in these vaccination groups. However, there was no significant difference between these two groups. A vaccination therapy using DCs co-transduced with the TAA gene and Th 1-type cytokine genes, especially the IL-12 gene, is ideal for immunotherapy in terms of the activation of DCs, NK cells, CD4+ T cells and CD8+ T cells, and may be useful in the clinical application of a cancer vaccine therapy.

Adenoviridae↗

PubMed2005

Dendritic cells transduced with tumor-associated antigen gene elicit potent therapeutic antitumor immunity: comparison with immunodominant peptide-pulsed DCs.

Several studies have shown that vaccine therapy using dendritic cells (DCs) pulsed with specific tumor antigen peptides can effectively induce antitumor immunity. Peptide-pulsed DC therapy is reported to be effective against melanoma, while it is still not sufficient to show the antitumor therapeutic effect against epithelial solid tumors such as gastrointestinal malignancies. Recently, it has been reported that vaccine therapy using DCs transduced with a surrogate tumor antigen gene can elicit a potent therapeutic antitumor immunity. In this study, we investigated the efficacy of vaccine therapy using DCs transduced with the natural tumor antigen in comparison with peptide-pulsed DCs. DCs derived from murine bone marrow were adenovirally transduced with murine endogenous tumor antigen gp70 gene, which is expressed in CT26 cells, or DCs were pulsed with the immunodominant peptide AH-1 derived from gp70. We compared these two cancer vaccines in terms of induction of antigen-specific cytotoxic T lymphocyte (CTL) responses, CD4+ T cell response against tumor cells, migratory capacity of DCs and therapeutic immunity in vivo. The cytotoxic activity of splenocytes against CT26 and Meth-A pulsed with AH-1 in mice immunized with gp70 gene-transduced DCs was higher than that with AH-1-pulsed DCs. CD4+ T cells induced from mice immunized with gp70 gene-transduced DCs produced higher levels of IFN-gamma by stimulation with CT26 than those from mice immunized with AH-1-pulsed DCs (p < 0.0001), and it was suggested that DCs transduced with tumor-associated antigen (TAA) gene induced tumor-specific CD4+ T cells, and those CD4+ T cells played a critical role in the priming phase of the CD8+ T cell response for the induction of CD8+ CTL. Furthermore, DCs adenovirally transduced with TAA gene showed an enhancement of expression of CC chemokine receptor 7 and improved the migratory capacity to draining lymph nodes. In subcutaneous models, the vaccination using gp70 gene-transduced DCs provided a remarkably higher therapeutic efficacy than that using AH-1-pulsed DCs. These results suggested that vaccine therapy using DCs adenovirally transduced with TAA gene can elicit potent antitumor immunity, and may be useful for clinical application.

Adenocarcinoma↗

PubMed2005

Reduced word-repetition effect in the event-related potentials of thought-disordered patients with schizophrenia.

Repetition effect in event-related potentials (ERPs) was studied in 10 non-thought-disordered (non-TD) patients with schizophrenia, 8 thought-disordered (TD) patients with schizophrenia, and 10 normal control subjects while they performed a semantic categorization task with incidental word repetitions. All patients were in a stable or partially remitted stage. Although both healthy control and non-TD groups produced more positive ERPs to the repeated words than to the new words (ERP repetition effect) for 250-500 ms, the TD group did not show the ERP repetition effect. These findings suggest that the abnormal attenuation of the ERP repetition effect during semantic processing may be more prominent in schizophrenic patients with thought disorder than in those without the symptom.

Adult↗

PubMed2005

The role of cognitive-motor function in precipitation and inhibition of epileptic seizures.

PURPOSE: To examine the effects of cognitive-motor function on EEG discharges and the neuropsychological mechanisms of seizure induction in patients sensitive to cognitive-motor tasks. METHODS: Four hundred eighty patients with epilepsies were subjected to cognitive tasking, termed "neuropsychological EEG activation (NPA)." It consisted of reading, speaking, writing, written calculation, mental calculation, and spatial construction. Furthermore, patients showing a provocative NPA effect were subjected to a detailed NPA protocol to identify the possible precipitating factors, which consisted of simple hand movements, action programming requiring hand movement, and thinking activity not requiring hand movement. RESULTS: NPA had an inhibitory effect on EEG discharges in 133 (63.9%) of 208 patients with discharges in the awake EEG. Conversely, NAP had a provocative effect in 38 (7.9%) of 480 patients. In 32 of the 38 patients, the precipitating factor was action programming. Among them, five showed a precipitating factor restricted to linguistic activity, and the remaining 27 were affected by various action-programming factors including both linguistic and praxic activities. In four of 38 patients, the precipitating factor was thinking, predominantly linguistic tasks in one patient and spatial tasks in three patients. No patient had a precipitating factor identified as motor activity. CONCLUSIONS: These results suggest that cognitive-motor function has an inhibitory effect on EEG discharges in the majority of epilepsy patients and a provocative effect in some patients, and that seizures of the patients showing a provocative NPA effect are precipitated by action programming or thinking activity.

Adolescent↗

PubMed2005

[Cognitive dysfunction and electroencephalogram in schizophrenia].

Recent developments in neuroscience, especially in neuropsychology and neuroimaging, have shed light on cognitive dysfunction in schizophrenia. Cognitive dysfunction may be the underlying basis of schizophrenic symptoms and also the vulnerability marker such as an endophenotype used in genetic studies. Among various cognitive functions, attention is currently focused on "social cognition" as a new realm of research which it may determine the social and occupational abilities of patients with schizophrenia. Recent studies indicate that the second-generation antipsychotics may improve some aspects of cognitive dysfunction in schizophrenia. This urges us to reveal whether such drugs also improve the long-term prognosis as well as quality of life of the patients. Although cognitive function has usually been evaluated by neuropsychological tests, it is advisable to employ electroencephalogram especially event-related potential, which has high time resolution, in combination with neuroimaging with high spatial resolution. In this paper, studies with event-related potentials including P50, MMN, Nd, NA, P300, and N400 are reviewed and we propose a pathophysiological model of schizophrenia from the viewpoint of information processing. The model consists of a controlled processing system (e. g., perceptual organization, and semantic integration) and regulatory system which is mainly automatic processing and enables the controlled processing to be efficient. We postulate that both systems will be primarily affected in schizophrenia and that disruptions in the regulatory system from any cause will impose. further burden on the controlled system and lead to psychosis. Finally, comprehensive and sophisticated assessment of these systems will be required in schizophrenia research.

Antipsychotic Agents↗

PubMed2005

[Mechanism of the bone destruction in rheumatoid arthritis].

Rheumatoid arthritis (RA) is characterized by the presence of inflammatory synovitis accompanied by cartilage and bone destruction. Histological examination of RA pannus shows a number of osteoclasts on the surface of the destructed bone. RA synovial tissues produce a variety of proinflammatory cytokines and growth factors that may increase osteoclast formation, activity, and/or survival. Synovial fibroblasts from RA patients express high levels of RANKL, which is essential for the differentiation of osteoclasts, and therefore, RANKL can be a good therapeutic target of joint destruction in RA.

Arthritis, Rheumatoid↗

PubMed2004

Adenoviral-mediated gene transduction of the hepatocyte growth factor (HGF) antagonist, NK4, suppresses peritoneal metastases of gastric cancer in nude mice.

The competitive inhibitory effects of NK4 (a specific hepatocyte growth factor (HGF)-antagonist) on the interaction between HGF and the c-Met/HGF receptor has been shown in HGF-mediated invasion of some distinct types of human cancer cells. Furthermore, NK4 has inhibitory effects on the angiogenic pathways driven by basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), as well as by HGF. In this study, to evaluate the therapeutic efficacy of adenoviral-mediated NK4 gene treatment, we employed animal models of peritoneal metastasis using two gastric cancer cell lines, the strongly c-Met expressing MKN45 cell line and the weakly c-Met-expressing cell line, TMK1. In both models, the total number and weight of peritoneal tumours per mouse and ascites treated early with AxCANK4 (administered 3 times 2, 7 and 12 days after the tumour inoculation) were significantly reduced compared with those treated with phosphate-buffered solution (PBS) and AxCALacZ (P < 0.05). In Factor-VIII-related-antigen-stained sections from peritoneal metastatic tumours, the inhibition of intratumour vessels was observed in tissues from tumours of MKN45 and TMK1 treated with AxCANK4. We also compared the therapeutic effect of early AxCANK4 treatment with that of late treatment (at 7, 12 and 17 days). Peritoneal metastases and ascites treated late with AxCANK4 showed less of an improvement than those treated early with AxCANK4 in both models. In addition, the inhibitory effect of cisplatin (CDDP) on peritoneal metastasis was significantly enhanced by AxCANK4, suggesting that the combination of intraperitoneal (i.p.) chemotherapy with NK4 gene therapy might be effective, even in cases of advanced peritoneal metastasis from gastric cancer. To conclude, these results show clearly that NK4 gene therapy inhibits peritoneal metastases from gastric cancer, regardless of the level of c-Met/HGF receptor expression in the tumour cells, and especially in the early stages of peritoneal metastasis.

Adenoviridae↗

PubMed2003

Clinical benefit of chemosensitivity test for patients with regional lymph node-positive esophageal squamous cell carcinoma.

BACKGROUND AND OBJECTIVES: Patients who have undergone resection for lymph node-positive esophageal squamous cell carcinoma are at high risk of recurrence and early death. The role of the postoperative adjuvant chemotherapy in this population needs to be determined. The present study was designed to determine whether the chemosensitivity test in fresh human esophageal squamous cell carcinoma, using highly purified tumor cells, correlates with the clinical response. METHODS: A retrospective review of all patients with resected squamous cell carcinoma of the thoracic esophagus between 1993 and 2000 was performed. We determined the chemosensitivity for cisplatin (CDDP), 5-fluorouracil (5-FU), mitomycin C, and adriamycin in vitro in fresh human esophageal squamous cell carcinoma using the MTT assay. Regional lymph node-positive (N1) patients who received sequential postoperative chemotherapy were compared with lymph node positive patients who underwent surgery alone. RESULTS: A total of 50 patients were reviewed, and chemosensitivity tests were successfully performed in 46 patients: 20 patients received surgery alone (S group), and 26 patients received surgery plus postoperative chemotherapy (SC group) according to results of MTT assay using highly purified tumor cells. When the SC group was divided into an SC-low group (inhibition rate of CDDP + 5-FU was below 85%, n = 15) and an SC-high group (over 85%, n = 11), the SC-high group showed more significant survival prolongation than the S group or the SC-low group (P < 0.01). CONCLUSIONS: Our results suggest that the results of the conventional MTT assay may be useful in evaluating the optimum adjuvant chemotherapy for patients with regional lymph node positive (pN1) esophageal squamous cell carcinoma.

Aged↗

PubMed2003

Improvement of carcinoembryonic antigen-specific prodrug gene therapy for experimental colon cancer.

BACKGROUND: Improvement of tumor-specific gene expression is very important for achieving successful effects in prodrug gene therapy for advanced cancer with metastatic lesions. We used the Cre/loxP system for enhancing carcinoembryonic antigen (CEA)-specific prodrug gene therapy of cytosine (CD)/5-fluorocytosine (5-FC) for the treatment of a colon cancer model accompanied with liver metastases. METHODS: Orthotopic colon cancer models were developed. Seven days later, adenovirus vector (3 x 10(9) pfu)was injected into the abdominal cavity, and 5-FC was administered for the next 10 days. RESULTS: In these models, the double administration of AxCEANCre expressing Cre recombinase under the control of the CEA promoter, and AxCALNLCD expressing the CD gene under the control of the CAG promoter by the Cre-mediated switching system, completely inhibited liver metastases, and significantly reduced primary tumor volume compared to the administration of Mock or AxCEACD (P <.001). The survival periods of the mice treated with AxCEANCre and AxCALNLCD were longer than mice treated with Mock or AxCEACD, and longer than the mice treated with AxCACD (P <.05). CONCLUSIONS: The enhanced CEA-specific prodrug gene therapy using the Cre/loxP system was useful for the treatment of advanced colon cancer with liver metastases, implicating clinical application.

Adenoviridae↗

PubMed2003

Intensification of antitumor effect by T helper 1-dominant adoptive immunogene therapy for advanced orthotopic colon cancer.

PURPOSE: T helper (Th) 1/Th2 balance, controlled by Th1 or Th2 cells producing cytokines, plays important roles in antitumor immunity. Interleukin-18 (IL-18) can act together with IL-12 in promoting the generation of IFN-gamma producing Th1 cells. The goal of this study was to determine whether cytotoxic T lymphocyte (CTL) secreted in a murine IL-18-induced Th1-dominant state inhibited the development of primary tumors and synchronous liver metastases in orthotopic colon cancer model. EXPERIMENTAL DESIGN: Murine IL-18 gene was transduced into activated T lymphocytes by an adenovirus vector encoding IL-18 (AdIL-18) liposome complex method. Efficacy of adoptive immunogene therapy using AdIL-18 with or without IL-12 was tested in advanced orthotopic xenograft of murine colon cancer. To elucidate the mechanism responsible for the adoptive immunogene therapy, serum IL-4, IL-6, IFN-gamma, and tumor necrosis factor alpha production in Th1/Th2 cytokine balance and quantification of tumor vascularity were investigated. RESULTS: By a modified method of adenoviral gene transduction, T lymphocytes achieved efficient IL-18 production without cell toxicity. Against orthotopic colon cancer, when combined with low dose of recombinant (r) IL-12 (AdIL-18-CTL/rIL-12), the therapeutic efficacy showed much smaller tumors with no liver metastases and no disseminated tumors. There was a significant difference in the volume of primary tumors and the number of liver metastases compared with the group treated with AdIL-18-CTL alone or other group (P < 0.01). In addition, the median survival time of the group treated with AdIL-18-CTL was 53.7 +/- 5.8 days and that of AdIL-18-CTL/rIL-12 was 78.4 +/- 6.1 days, which was also a significant difference (P < 0.01). These antitumor mechanisms were involved with Th1-dominant response in serum Th1/Th2 cytokine balance and suppression of neovascularization at primary tumor site. CONCLUSION: These data suggest that a strategy of Th1/Th2 balance-based adoptive immunogene therapy might be useful for advanced cancer patients.

Adenoviridae↗

PubMed2002

Esophageal intramural pseudodiverticulosis with Mallory-Weiss syndrome: report of a case.

A 62-year-old man with a chief complaint of coughing up blood was revealed to have Mallory-Weiss syndrome with arterial bleeding by gastrointestinal endoscopy at the esophagogastric junction, and two teardrop-shaped fissures were found longitudinally extending into the muscle layer. Endoscopic treatment with ethanol injection and the administration of a thrombin solution spray failed to control the arterial bleeding. Hemostasis was finally archived by suturing the fissures under an open laparotomy. A postoperative barium esophagogram showed multiple flask-shaped outpouchings in the thoracic esophagus, and a diagnosis of esophageal intramural pseudodiverticulosis (EIPD) was thus made. EIPD is usually accompained with esophageal strictures but esophageal bleeding is rare.

Diagnosis, Differential↗

PubMed2002

Cytoskeletal inhibitors, anti-adhesion molecule antibodies, and lectins inhibit hepatocyte spheroid formation.

We investigated the role of cytoskeletons, adhesion molecules, membrane-glycosylations, and proteoglycans in forming the shape of adult rat hepatocyte spheroids. Isolated hepatocytes were cultured on dishes coated with chondroitin sulfate phosphatidyl ethanolamine (CS-PE). Spheroid-forming ability was observed after adding cytoskeletal inhibitors (cytochalasin D, colchicine, okadaic acid, mycalolide B), anti-adhesion molecule antibodies (anti-E-cadherin, anti-connexin 32, anti-zo-1), a glycosphingolipid synthetic inhibitor (N-butyldeoxynojirimycin), a proteoglycan synthetic inhibitor (p-nitrophenyl-beta-D-xylopyranoside), and several lectins. Localization of actin was studied using confocal microscopy after rhodamine-phalloidin staining. Adding cytoskeletal inhibitors on the initial day resulted in weakly clustered cell aggregates rather than smoothly formed spheroids. These effects disappeared at lower reagent concentrations. When reagents were added on day 3, after the formation of spheroids, only mycalolide B was associated with an irregular spheroid surface; the others had no effect. Adding the anti-E-cadherin, anti-connexin 32 on the initial day showed inhibition of spheroid formation, but anti-zo-1 and proteoglycan synthetic inhibitor had no effects. Among the several lectins, only Wheat Germ Agglutinin (WGA), Ricinus communis Agglutinin I (RCA-I), and Concanavalin A (ConA) showed inhibition. These results suggest that cytoskeletal conformation and some adhesion molecules are necessary to form spheroids. Based on the interactions between lectins and hepatocytes in the present study, hepatocytes appear to contain an N-linked complex or N-linked hybrid glycosylated chains.

Animals↗

PubMed2002

Dendritic cells genetically engineered to simultaneously express endogenous tumor antigen and granulocyte macrophage colony-stimulating factor elicit potent therapeutic antitumor immunity.

Recently, several studies have shown that vaccine therapy using dendritic cells (DCs) genetically engineered to express a surrogate tumor antigen can effectively induce antitumor immunity. In this study, murine bone marrow DCs were adenovirally transduced with murine endogenous tumor antigen gp70 expressed in CT26 cells and granulocyte macrophage colony-stimulating factor (GM-CSF), and we examined whether antigen-specific CTL responses and therapeutic immunity could be induced in mice immunized with those genetically modified DCs. The cytotoxic activity against CT26 in mice immunized with gp70-transduced DCs was significantly higher than that in control (P < 0.01) and was enhanced by GM-CSF-cotransduction (P < 0.001). GM-CSF gene transfer into DCs expressing tumor-associated antigen enhances CC chemokine receptor 7 expression on DCs, leading to improved migratory capacity of DCs to draining lymph nodes. Consequently, an effective antitumor immune response would be induced. Vaccination using gp70-transduced DCs provided remarkable therapeutic efficacy in s.c. models. Moreover, it could be sufficiently augmented by GM-CSF-cotransduction of DCs. These results support that vaccination therapy using DCs simultaneously transduced with tumor-associated antigen can elicit potent CTL response, and GM-CSF-cotransduction of DCs could optimize therapeutic response. Further investigation is needed to optimize this vaccine therapy to achieve the obvious benefit in clinical application.

Adenoviridae↗