scholarly journals Reduction-Sensitive Protein Nanogels Enhance Uptake of Model and Tumor Lysate Antigens In Vitro by Mouse- and Human-Derived Dendritic Cells

2021 ◽  
Author(s):  
Cristiana Berti ◽  
Alice Boarino ◽  
Michele Graciotti ◽  
Lisa P. E. Bader ◽  
Lana E. Kandalaft ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Tumor Lysate ◽  
Lysate Antigens

scholarly journals PGE2 Is Crucial for the Generation of FAST Whole- Tumor-Antigens Loaded Dendritic Cells Suitable for Immunotherapy in Glioblastoma

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 215
Author(s):  
Sara Nava ◽  
Daniela Lisini ◽  
Simona Frigerio ◽  
Simona Pogliani ◽  
Serena Pellegatta ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Large Scale ◽  
Tumor Antigens ◽  
Labor Cost ◽  
Small Scale ◽  
Clinical Grade ◽  
Tumor Lysate

Dendritic cells (DC) are the most potent antigen-presenting cells, strongly inducers of T cell-mediated immune responses and, as such, broadly used as vaccine adjuvant in experimental clinical settings. DC are widely generated from human monocytes following in vitro protocols which require 5–7 days of differentiation with GM-CSF and IL-4 followed by 2–3 days of activation/maturation. In attempts to shorten the vaccine’s production, Fast-DC protocols have been developed. Here we reported a Fast-DC method in compliance with good manufacturing practices for the production of autologous mature dendritic cells loaded with antigens derived from whole tumor lysate, suitable for the immunotherapy in glioblastoma patients. The feasibility of generating Fast-DC pulsed with whole tumor lysate was assessed using a series of small-scale cultures performed in parallel with clinical grade large scale standard method preparations. Our results demonstrate that this Fast protocol is effective only in the presence of PGE2 in the maturation cocktail to guarantee that Fast-DC cells exhibit a mature phenotype and fulfill all requirements for in vivo use in immunotherapy approaches. Fast-DC generated following this protocol were equally potent to standard DC in inducing Ag-specific T cell proliferation in vitro. Generation of Fast-DC not only reduces labor, cost, and time required for in vitro clinical grade DC development, but can also minimizes inter-preparations variability and the risk of contamination.

scholarly journals Murine dendritic cells pulsed with whole tumor lysates mediate potent antitumor immune responsesin vitroandin vivo

1998 ◽  
Vol 95 (16) ◽  
pp. 9482-9487 ◽  
Author(s):  
R. C. Fields ◽  
K. Shimizu ◽  
J. J. Mulé
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Tumor Rejection ◽  
Autologous Tumor ◽  
Tumor Lysate ◽  
Cell Reactivity ◽  
Pulsed Dc ◽  
Pediatric Cancer Patients

The highly efficient nature of dendritic cells (DC) as antigen-presenting cells raises the possibility of uncovering in tumor-bearing hosts very low levels of T cell reactivity to poorly immunogenic tumors that are virtually undetectable by other means. Here, we demonstrate thein vitroandin vivocapacities of murine bone marrow-derived, cytokine-driven DC to elicit potent and specific anti-tumor responses when pulsed with whole tumor lysates. Stimulation of naive spleen-derived T cells by tumor lysate-pulsed DC generated tumor-specific proliferative cytokine release and cytolytic reactivitiesin vitro. In addition, in two separate strains of mice with histologically distinct tumors, s.c. injections of DC pulsed with whole tumor lysates effectively primed these animals to reject subsequent lethal challenges with viable parental tumor cells and, important to note, also mediated significant reductions in the number of metastases established in the lungs. Tumor rejection depended on host-derived CD8+T cells and, to a lesser extent, CD4+T cells. Spleens from mice that had rejected their tumors contained specific precursor cytotoxic T lymphocytes. The use of whole tumor lysates as a source of tumor-associated antigen(s) for pulsing of DC circumvents several limitations encountered with other methods as well as provides certain distinct advantages, which are discussed. These data serve as rationale for our recent initiation of a phase I clinical trial of immunization with autologous tumor lysate-pulsed DC in adult and pediatric cancer patients.

scholarly journals The maturation of murine bone marrow-derived dendritic cells by tumor lysate uptake in vitro is not essential for cancer immunotherapy

2005 ◽  
Vol 4 (12) ◽  
pp. 1331-1335 ◽  
Author(s):  
Sung-Chil Woo ◽  
Gi-Young Kim ◽  
Chang-Min Lee ◽  
Dong-Oh Moon ◽  
Tae-Hyung Lee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cells ◽  
Cancer Immunotherapy ◽  
Tumor Lysate ◽  
Murine Bone Marrow

scholarly journals Induction of cellular immunity in a parathyroid carcinoma treated with tumor lysate-pulsed dendritic cells

2000 ◽  
pp. 300-306 ◽  
Author(s):  
M Schott ◽  
J Feldkamp ◽  
D Schattenberg ◽  
T Krueger ◽  
C Dotzenrath ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Dendritic Cells ◽  
Parathyroid Carcinoma ◽  
Interleukin 4 ◽  
Delayed Type Hypersensitivity ◽  
Dendritic Cell Vaccination ◽  
Tumor Lysate

BACKGROUND: Cytotoxic T-lymphocyte-mediated tumor immunity against major histocompatibility antigen class II-negative tumors requires help from CD4(+) T-cells. The major antigen presenting cells for CD4(+) cell activation are dendritic cells. Studies in mice and humans have demonstrated the potent capacity of these cells to induce specific antitumor immunity. OBJECTIVE: To control the growth of a metastasized parathyroid carcinoma, by immunizing a patient with tumor lysate and parathyroid hormone-pulsed dendritic cells. DESIGN AND METHODS: Mature dendritic cells were generated from peripheral blood monocytes in the presence of granulocyte/macrophage colony-stimulating factor, interleukin-4 and tumor necrosis factor alpha. Antigen-loaded dendritic cells were delivered by subcutaneous and intralymphatical injections. After five cycles, we added keyhole limpet hemocyanin (KLH) as a CD4(+) helper antigen. RESULTS: After 10 vaccinations, a specific cellular immune response to tumor lysate was observed. In vitro T-cell proliferation assays revealed a dose-dependent stimulation index of 1.8-5.7 compared with 0.9-1.1 before vaccination. In vivo immune response was demonstrated by positive delayed-type hypersensitivity toward tumor lysate. Intradermal injection of tumor lysate resulted in an erythema and induration, suggesting the efficient generation of tumor lysate-specific memory T-cells. CONCLUSIONS: These data indicate that dendritic cell vaccination can induce in vitro and in vivo responses in a highly malignant endocrine carcinoma. Regardless of the clinical outcome of our patient, this approach might be generally applicable to other advanced, radio- and chemotherapy-resistant endocrine malignancies, such as adrenal carcinomas and metastasized medullary and anaplastic thyroid carcinomas.

Vaccination of patients with cutaneous T-cell lymphoma using intranodal injection of autologous tumor-lysate–pulsed dendritic cells

Blood ◽  
2003 ◽  
Vol 102 (7) ◽  
pp. 2338-2344 ◽  
Author(s):  
Tanja Maier ◽  
Adrian Tun-Kyi ◽  
Anatoli Tassis ◽  
Karl-Peter Jungius ◽  
Günter Burg ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Delayed Type Hypersensitivity ◽  
Interferon Α ◽  
Autologous Tumor ◽  
Cutaneous T Cell Lymphoma ◽  
Tumor Lysate

Abstract Cutaneous T-cell lymphoma (CTCL) is a lymphoproliferative skin disease with limited therapeutic options. Ten CTCL patients were treated with once-weekly intranodal injection of 1 × 106 mature monocyte-derived dendritic cells (DCs) pulsed with 100 μg/mL tumor lysate protein equivalent and keyhole limpet hemocyanin (50 μg/mL). Tumor-specific delayed-type hypersensitivity (DTH) reactions developed in 8 of 8 patients challenged with tumor-lysate-pulsed DCs and in 3 of 8 patients challenged with tumor lysate alone. Three of 5 patients showed significant tumor-lysate-specific increases of in vitro peripheral blood lymphocyte proliferation coinciding with increased interferon-α (IFN-α) production. Five of 10 (50%) patients had objective responses. Four patients had partial responses (PRs). Two are still in PR, and the other 2 patients had a mean PR duration of 10.5 months. One patient had a complete response (CR) for 19 months that is ongoing. The remaining 5 patients had progressive disease. In the 5 responder patients, 6.8 ± 1.4 vaccinations were necessary to induce an objective clinical response. Response was associated with low tumor burden. Continuation of vaccinations with new tumor lysate derived from progressive lesions reinduced treatment responses in 2 patients in PR. Selected patients had massive infiltration of CD8+ and TIA+ cytotoxic T cells at the site of regressing lesions and molecular remission after therapy. Intranodal injection of autologous tumor-lysate-pulsed DCs is well-tolerated and achieves immunologic and objective clinical responses in selected CTCL patients. (Blood. 2003;102:2338-2344)

scholarly journals CD14 Expressing Precursors Give Rise to Highly Functional Conventional Dendritic Cells for Use as Dendritic Cell Vaccine

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3818
Author(s):  
Maud Plantinga ◽  
Denise A. M. H. van den Beemt ◽  
Ester Dünnebach ◽  
Stefan Nierkens
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Cord Blood ◽  
T Cell Activation ◽  
Cell Activation ◽  
Ex Vivo ◽  
Dendritic Cell Vaccine ◽  
Cell Vaccine ◽  
Activated T Cells

Induction of long-lasting immunity by dendritic cells (DCs) makes them attractive candidates for anti-tumor vaccination. Although DC vaccinations are generally considered safe, clinical responses remain inconsistent in clinical trials. This initiated studies to identify subsets of DCs with superior capabilities to induce effective and memory anti-tumor responses. The use of primary DCs has been suggested to overcome the functional limitations of ex vivo monocyte-derived DCs (moDC). The ontogeny of primary DCs has recently been revised by the introduction of DC3, which phenotypically resembles conventional (c)DC2 as well as moDC. Previously, we developed a protocol to generate cDC2s from cord blood (CB)-derived stem cells via a CD115-expressing precursor. Here, we performed index sorting and single-cell RNA-sequencing to define the heterogeneity of in vitro developed DC precursors and identified CD14+CD115+ expressing cells that develop into CD1c++DCs and the remainder cells brought about CD123+DCs, as well as assessed their potency. The maturation status and T-cell activation potential were assessed using flow cytometry. CD123+DCs were specifically prone to take up antigens but only modestly activated T-cells. In contrast, CD1c++ are highly mature and specialized in both naïve as well as antigen-experienced T-cell activation. These findings show in vitro functional diversity between cord blood stem cell-derived CD123+DC and CD1c++DCs and may advance the efficiency of DC-based vaccines.

scholarly journals Tumor cytotoxicity and immunogenicity of a novel V-jet neon plasma source compared to the kINPen

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lea Miebach ◽  
Eric Freund ◽  
Stefan Horn ◽  
Felix Niessner ◽  
Sanjeev Kumar Sagwal ◽  
...  
Keyword(s):  
Cell Death ◽  
Dendritic Cells ◽  
Cancer Cells ◽  
Treatment Time ◽  
Plasma Source ◽  
In Vivo Model ◽  
Antitumor Effects ◽  
Plasma Device

AbstractRecent research indicated the potential of cold physical plasma in cancer therapy. The plethora of plasma-derived reactive oxygen and nitrogen species (ROS/RNS) mediate diverse antitumor effects after eliciting oxidative stress in cancer cells. We aimed at exploiting this principle using a newly designed dual-jet neon plasma source (Vjet) to treat colorectal cancer cells. A treatment time-dependent ROS/RNS generation induced oxidation, growth retardation, and cell death within 3D tumor spheroids were found. In TUM-CAM, a semi in vivo model, the Vjet markedly reduced vascularized tumors' growth, but an increase of tumor cell immunogenicity or uptake by dendritic cells was not observed. By comparison, the argon-driven single jet kINPen, known to mediate anticancer effects in vitro, in vivo, and in patients, generated less ROS/RNS and terminal cell death in spheroids. In the TUM-CAM model, however, the kINPen was equivalently effective and induced a stronger expression of immunogenic cancer cell death (ICD) markers, leading to increased phagocytosis of kINPen but not Vjet plasma-treated tumor cells by dendritic cells. Moreover, the Vjet was characterized according to the requirements of the DIN-SPEC 91315. Our results highlight the plasma device-specific action on cancer cells for evaluating optimal discharges for plasma cancer treatment.

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