scholarly journals Carthamus tinctoriusEnhances the Antitumor Activity of Dendritic Cell Vaccines via Polarization toward Th1 Cytokines and Increase of Cytotoxic T Lymphocytes

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Jia-Ming Chang ◽  
Le-Mei Hung ◽  
Yau-Jan Chyan ◽  
Chun-Ming Cheng ◽  
Rey-Yuh Wu
Keyword(s):  
Dendritic Cell ◽  
T Lymphocytes ◽  
Antitumor Activity ◽  
Cytotoxic T Lymphocytes ◽  
Tumor Antigens ◽  
Ex Vivo ◽  
Cytokine Secretion ◽  
Tumor Lysate ◽  
Dc Vaccine ◽  
Pulsed Dc

Carthamus tinctorius(CT), also named safflower, is a traditional Chinese medicine widely used to improve blood circulation. CT also has been studied for its antitumor activity in certain cancers. To investigate the effects of CT on the dendritic cell (DC)-based vaccine in cancer treatment, cytokine secretion of mouse splenic T lymphocytes and the maturation of DCs in response to CT were analyzed. To assess the antitumor activity of CT extract on mouse CD117+(c-kit)-derived DCs pulsed with JC mammal tumor antigens, the JC tumor was challenged by the CT-treated DC vaccinein vivo. CT stimulated IFN-γand IL-10 secretion of splenic T lymphocytes and enhanced the maturation of DCs by enhancing immunological molecule expression. When DC vaccine was pulsed with tumor antigens along with CT extract, the levels of TNF-αand IL-1βwere dramatically increased with a dose-dependent response and more immunologic and co-stimulatory molecules were expressed on the DC surface. In addition, CT-treated tumor lysate-pulsed DC vaccine reduced the tumor weight in tumor-bearing mice by 15.3% more than tumor lysate-pulsed DC vaccine without CT treatment. CT polarized cytokine secretion toward the Th1 pathway and also increased the population of cytotoxic T lymphocytesex vivo. In conclusion, CT activates DCs might promote the recognition of antigens and facilitate antigen presentation to Th1 immune responses.

scholarly journals Dendritic cell–based immunotherapy targeting Wilms’ tumor 1 in patients with recurrent malignant glioma

2015 ◽  
Vol 123 (4) ◽  
pp. 989-997 ◽  
Author(s):  
Keiichi Sakai ◽  
Shigetaka Shimodaira ◽  
Shinya Maejima ◽  
Nobuyuki Udagawa ◽  
Kenji Sano ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Malignant Glioma ◽  
Stable Disease ◽  
Wilms Tumor ◽  
Malignant Gliomas ◽  
Tumor Lysate ◽  
Dc Vaccine ◽  
Pulsed Dc ◽  
Wilms Tumor 1 ◽  
Vaccination Therapy

OBJECT Dendritic cell (DC)-based vaccination is considered a potentially effective therapy against advanced cancer. The authors conducted a Phase I study to investigate the safety and immunomonitoring of Wilms’ tumor 1 (WT1)-pulsed DC vaccination therapy for patients with relapsed malignant glioma. METHODS WT1-pulsed and/or autologous tumor lysate-pulsed DC vaccination therapy was performed in patients with relapsed malignant gliomas. Approximately 1 × 107 to 2 × 107 pulsed DCs loaded with WT1 peptide antigen and/or tumor lysate were intradermally injected into the axillary areas with OK-432, a streptococcal preparation, at 2-week intervals for at least 5–7 sessions (1 course) during an individual chemotherapy regimen. RESULTS Ten patients (3 men, 7 women; age range 24–64 years [median 39 years]) with the following tumors were enrolled: glioblastoma (6), anaplastic astrocytoma (2), anaplastic oligoastrocytoma (1), and anaplastic oligodendroglioma (1). Modified WT1 peptide–pulsed DC vaccine was administered to 7 patients, tumor lysate-pulsed DC vaccine to 2 patients, and both tumor lysate–pulsed and WT1-pulsed DC vaccine to 1 patient. The clinical response was stable disease in 5 patients with WT1-pulsed DC vaccination. In 2 of 5 patients with stable disease, neurological findings improved, and MR images showed tumor shrinkage. No serious adverse events occurred except Grade 1–2 erythema at the injection sites. WT1 tetramer analysis detected WT1-reactive cytotoxic T cells after vaccination in patients treated with WT1-pulsed therapy. Positivity for skin reaction at the injection sites was 80% (8 of 10 patients) after the first session, and positivity remained for these 8 patients after the final session. CONCLUSIONS This study of WT1-pulsed DC vaccination therapy demonstrated safety, immunogenicity, and feasibility in the management of relapsed malignant gliomas.

Reinforcement of Cancer Immunotherapy by Adoptive Transfer of Cblb-Deficient Cytotoxic T Lymphocytes Combined with a Dendritic Cell Vaccine

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 957-957
Author(s):  
Christina Lutz-Nicoladoni ◽  
Patrizia Stoizner ◽  
Magdalena Pircher ◽  
Stephanie Wallner ◽  
Anna Maria Wolf ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Dendritic Cell ◽  
Cancer Immunotherapy ◽  
Cytotoxic T Lymphocytes ◽  
Adoptive Transfer ◽  
Ex Vivo ◽  
Dc Vaccine

Abstract Abstract 957 Introduction: Various approaches to induce immunological rejection of tumors including transfer of autologous tumor infiltrating lymhocytes (TIL) after ex vivo clonal expansion or application of ex vivo transduced antigen specific T cell (TCR) transgenic T cells have been elaborated. In general, adoptive T cell transfer (ATC) has been combined with lympho-depleting agents (e.g. cyclophosphamide). However, the therapeutic efficacy of these cancer immunotherapy approaches is limited due to insufficient in vivo activation, expansion and survival of transferred effector immune cells, which is mainly due to suppressive mileu signals and immune evasion mechanisms induced by TGF-β. The E3 ubiquitin ligase Cbl-b is a key regulator of T cell activation and is assumed to confer TGF-β resistance. Thus we performed a proof-of-concept study evaluating Cbl-b targeting as “intracellular adjuvant” strategy to improve ATC for cancer immunotherapy. Material and Methods: We first tested the in vitro sensitivity of CTL towards TGF-β mediated immuno-suppressive cues and then in vivo evaluated the anti-tumor reactivity of cblb-deficient cytotoxic T lymphocytes (CTL) in murine tumor models alone or in combination with a dendritic cell (DC) vaccine. Results: Cblb-deficient CTL are hyper-responsive to TCR/CD28-stimulation in vitro and protected from the negative cues induced by TGF-β as determined by quantification fo IFN-g secretion and quantification of their proliferative capacity. Unexpectedly, adoptive transfer of polyclonal, non TCR-transgenic cblb-deficient CD8+ CTL, however, is not sufficient to reject B16ova or EG7 tumors in vivo, which is in clear contrast to previous reports using lymphopenic animals receiving adoptively transferred TCR-transgenic T cells. Thus, we next evaluated in vivo re-activation of adoptively transferred cblb-deficient T cells by a DC vaccine (i.e. SIINFEKL-pulsed DC). In strict contrast to ATC monotherapy, this approach now markedly delays tumor outgrowth and significantly increase survival rates, which is paralleled by an increased CTL infiltration rate to the tumor site and an enrichment of ova-specific and IFN-g-secreting CTL in the draining lymph nodes. Moreover, compared to wild-type CTL, cblb-deficient mice vaccinated with the DC vaccine show an increased cytolytic activity in vivo. Conclusions: In summary, we provide experimental evidence that genetic inactivation of cblb in polyclonal, non-TCR transgenic adoptively transferred CTL might serve as a novel “adjuvant approach”, suitable to augment the effectiveness of anti-cancer immunotherapies using ATC in immune-competent recipients. Disclosures: No relevant conflicts of interest to declare.

Induction of myeloma-specific cytotoxic T lymphocytes ex vivo by CD40-activated B cells loaded with myeloma tumor antigens

2009 ◽  
Vol 88 (11) ◽  
pp. 1113-1123 ◽  
Author(s):  
Sang-Ki Kim ◽  
Thanh-Nhan Nguyen Pham ◽  
Tuyet Minh Nguyen Hoang ◽  
Hyun-Kyu Kang ◽  
Chun-Ji Jin ◽  
...  
Keyword(s):  
B Cells ◽  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Tumor Antigens ◽  
Ex Vivo ◽  
Activated B Cells

scholarly journals Ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of liposomal antigen and CpG-ODN improved PD-1 blockade immunotherapy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mona Yazdani ◽  
Zahra Gholizadeh ◽  
Amin Reza Nikpoor ◽  
Nema Mohamadian Roshan ◽  
Mahmoud Reza Jaafari ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
Low Dose ◽  
Ex Vivo ◽  
Dependent Manner ◽  
Cpg Odn ◽  
Dc Vaccine ◽  
Pulsed Dc ◽  
Anti Cancer ◽  
Anti Tumor Activity

AbstractLack of pre-existing tumor infiltrated T cells resulting in resistance to programmed cell death protein 1 (PD-1) blockade therapies can be solved by combining with anti-cancer vaccines and CpG-ODN in increasing T cell expansion and infiltration. Therefore, we prepared an ex vivo dendritic cell-based (DC) vaccine pulsed with a low dose of either liposomal or non-liposomal gp100 antigen (2.8 µg) plus CpG-ODN (800 ng) formulations and evaluated its anti-tumor activity in combination with anti-PD-1 therapy. Our results showed a combination of liposomal peptide plus CpG-ODN pulsed DC with anti-PD-1 antibody was more efficacious, as evidenced by a significant increase in Teff/Treg TILs with a marked fourfold elevation of IFN-γ expression level in the tumor site of treated mice which reversed resistance to PD-1 blockade in a CD8 T cell-dependent manner. Furthermore, this combination also led to a remarkable tumor remission and prolonged survival rate in melanoma-bearing mice compared to non-liposomal peptide plus CpG-ODN or single-treated liposomal peptide formulations. Our results provide essential insights to devise combining regimens to improve the efficacy of immune checkpoint blockers even by a low dose of peptide and CpG-ODN.

Dendritic cell vaccination in combination with TLR-7 agonist, imiquimod, following radio-chemotherapy for newly diagnosed glioblastoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2021-2021 ◽  
Author(s):  
L. M. Liau ◽  
R. M. Prins ◽  
S. K. Odesa ◽  
M. Y. Yang ◽  
M. S. Lin ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Tumor Antigens ◽  
Brain Mri ◽  
Dendritic Cell Vaccination ◽  
Autologous Tumor ◽  
Newly Diagnosed ◽  
Tumor Lysate ◽  
Pulsed Dc ◽  
Newly Diagnosed Glioblastoma ◽  
Radio Chemotherapy

2021 Background: Standard therapy for glioblastoma, which includes surgery followed by radiation and concurrent chemotherapy, creates a low tumor burden environment that could be ideal for immunotherapeutic approaches. We conducted a Phase I study to assess the safety and immunologic responses of tumor lysate-pulsed dendritic cell (DC) therapy plus topical imiquimod, in combination with standard radio-chemotherapy. Methods: Thirteen patients with newly diagnosed glioblastoma were immunized using autologous tumor lysate-pulsed DC. Each patient initially received 3 immunizations at 2-week intervals, following completion of a 6-week course of radio- chemotherapy. Four patients received 1 million DC, 4 received 5 million, and 5 received 10 million DC per immunization. Patients without tumor progression subsequently received booster vaccinations combined with topical administration of the TLR-7 agonist imiquimod. Immunologic responses to tumor antigens were monitored by HLA-restricted tetramer staining, CTL assays, and quantitation of T-regulatory cells. Clinical tumor growth was monitored by brain MRI scans every 2 months, and the primary clinical endpoint was 2-year survival. Results: All immunizations were well tolerated, with only mild side effects attributable to the DC vaccination and imiquimod adjuvant. Increased levels of CD8+ T cells reactive against tumor antigens, (e.g., gp100, TRP-2, her-2, survivin, and CMV antigens), were detected in 5 patients. Median PFS and OS have not been reached in this trial. To date, 6 of the 13 patients have progressed, and 4 of those have died. The median PFS to date is 18.1 mos. and median OS is 33.8 mos. This compares favorably with controls from the published literature, with a median PFS of 6.9 mos and OS of 14.6 mos. Conclusions: This study demonstrates the safety and clinical/immunologic effects of an autologous tumor lysate-pulsed DC vaccine for patients with newly diagnosed glioblastoma. The adjunctive use of the TLR-7 agonist imiquimod with DC vaccination appears to be non-toxic, and deserves further study. We demonstrate that this active immunotherapy strategy can generate antigen-specific immunologic responses in brain tumor patients following standard radio-chemotherapy. No significant financial relationships to disclose.

Generation and ex vivo expansion of cytotoxic T lymphocytes directed toward different types of leukemia or myelodysplastic cells using both HLA-matched and partially matched donors

2003 ◽  
Vol 31 (11) ◽  
pp. 1031-1038 ◽  
Author(s):  
Daniela Montagna ◽  
Rita Maccario ◽  
Enrica Montini ◽  
Roberto Tonelli ◽  
Daniela Lisini ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Cytotoxic T Lymphocytes ◽  
Ex Vivo ◽  
Ex Vivo Expansion ◽  
Different Types
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