Enhancement of antitumor immunity of dendritic cells pulsed with heat-treated tumor lysate in murine pancreatic cancer

Kim, Han Soo; Choo, Yee Shin; Koo, Taeseok; Bang, Seungmin; Oh, Tae Yun; Wen, Jing; Song, Si Young

doi:10.1016/j.imlet.2005.10.021

Cited by 37 publications

(35 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies have reported that DC vaccination of tumor bearing mice has led to increased tumor specific lysis by CD8 C T cells, expansion of IFNg secreting T cells, and tumor regression. [23][24][25] Targeting primary or metastatic lesions with intra-tumoral DC was effective in murine pancreatic cancer models and could be beneficial in human trials since a majority of patients are unresectable at the time of diagnosis. In one open label clinical trial, intra-tumoral injection of DC led to enhanced immunity and regression of tumor in several patients with pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

Chemo-immunotherapy mediates durable cure of orthotopic Kras^G12D/p53^−/−pancreatic ductal adenocarcinoma

Konduri

Halpert

et al. 2016

OncoImmunology

View full text Add to dashboard Cite

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States, exhibiting a five-year overall survival (OS) of only 7% despite aggressive standard of care. Recent advances in immunotherapy suggest potential application of immune-based treatment approaches to PDAC. To explore this concept further, we treated orthotopically established K-ras G12D /p53¡/¡ PDAC tumors with gemcitabine and a cell-based vaccine previously shown to generate durable cell-mediated (T H 1) immunity. Tumor progression was monitored by IVIS. The results indicated that the combination of chemotherapy and dendritic cell (DC) vaccination was effective in eliminating tumor, preventing metastasis and recurrence, and significantly enhancing OS. No animal that received the combination therapy relapsed, while mice that received gemcitabine-only or vaccine-only regimens relapsed and progressed. Analysis of circulating PBMC demonstrated that mice receiving the combination therapy exhibited significantly elevated levels of CD8 C

show abstract

Section: Discussionmentioning

confidence: 99%

Chemo-immunotherapy mediates durable cure of orthotopic Kras^G12D/p53^−/−pancreatic ductal adenocarcinoma

Konduri

Halpert

et al. 2016

OncoImmunology

View full text Add to dashboard Cite

show abstract

“…The use of orthotopic pancreatic cancer models in immunocompetent mice specifically benefits research on the interactions between the tumor and local microenvironment, especially in regard to immune aspects [20,21] . The Pan02 cell lines were established by Corbett et al [22] via injection of 3-methyl-cholanthrene into the pancreas of female C57BL/6 mice.…”

Section: Discussionmentioning

confidence: 99%

Establishment of an orthotopic pancreatic cancer mouse model: Cells suspended and injected in Matrigel

Jiang¹,

Lee²,

Wang³

et al. 2014

WJG

View full text Add to dashboard Cite

AIM:To establish an orthotopic mouse model of pancreatic cancer that mimics the pathological features of exocrine pancreatic adenocarcinoma. METHODS:Pan02 cells were suspended in low-temperature Matrigel and injected into the parenchyma of pancreatic tails of C57BL/6 mice, with cells suspended in phosphate buffered saline (PBS) serving as a control. Primary and implanted tumors were confirmed pathologically. The rate of tumor formation and intraperitoneal implantation in the two groups were compared at different time points after injection. Leakage and intraabdominal dispersion of Matrigel and PBS, both dyed with methylene blue, were compared after injection into the parenchyma of the pancreas. We observed adherence and proliferation in Pan02 cells suspended in Matrigel in vitro . We also compared the pathological manifestation of this orthotopic pancreatic cancer model in the head and tails of the pancreas. The characteristics of the origin of epithelial cells and exocrine markers of established orthotopic pancreatic tumors were confirmed using immunohistochemistry. RESULTS:Diluted Matrigel could form a gel drip in the pancreatic parenchyma, effectively preventing leakage from the injection site and avoiding dispersion in the abdominal cavity. Pan02 cells were able to adhere to a dish, proliferate, and migrate in the gel drip. The tumor formation rate in the Matrigel group was 100% at both 2 and 3 wk after injection, whereas it was 25.0% and 37.5% in the PBS group at 2 and 3 wk, respectively (P < 0.05). The intraperitoneal tumor implantation rate was 75.0% in the PBS group after 3 wk of injection, while it was 12.5% in the Matrigel group (P < 0.05). Hepatoduodenal ligament and duodenal invasions with obstructive jaundice and upper digestive obstruction with mesenteric lymph node metastasis were observed in the pancreatic head group. In the pancreatic tail group, spleen and gastric invasion were dominant, leading to retroperitoneal lymph nodes metastasis. Positive immunohistochemical staining of cytokeratin and negative staining of vimentin and chromogranin A confirmed that the orthotopic pancreatic tumor injected with Pan02 cells suspended in Matrigel was of epithelial origin and expressed exocrine markers of cancer. CONCLUSION:This method of low-temperature Matrigel suspension and injection is effective for establishing an orthotopic mouse model of pancreatic cancer. model in immunocompetent mice. The orthotopic pancreatic cancer models in the pancreatic head and tail both effectively mimic the relative pathological features of exocrine adenocarcinoma of the human pancreas. This model system will provide a platform for exploring new research outcomes for the effective treatment and management of pancreatic cancer.

show abstract

“…Previous studies in the Panc02 tumor model have shown that dendritic cells pulsed with tumor lysates can readily prime tumor-specific cytotoxic T-lymphocytes (36), which motivated our selection of a similar protocol for our study. We used Panc02 tumor lysates as the antigen source, with a pulsing strategy similar to that of protocols previously approved for clinical trials of dendritic cell vaccination (21,22,27,(36)(37)(38). Consistent with results of prior studies, this strategy yielded dose-dependent responses, with those mice receiving larger doses of pulsed dendritic cells experiencing better therapeutic outcomes (ie, slower tumor growth).…”

Section: Discussionmentioning

confidence: 99%

Antigen-loaded Dendritic Cell Migration: MR Imaging in a Pancreatic Carcinoma Model

Zhang¹,

Li²,

Procissi

et al. 2015

Radiology

View full text Add to dashboard Cite

).q RSNA, 2014 Purpose:To test the following hypotheses in a murine model of pancreatic cancer: (a) Vaccination with antigen-loaded iron-labeled dendritic cells reduces T2-weighted signal intensity at magnetic resonance (MR) imaging within peripheral draining lymph nodes (LNs) and (b) such signal intensity reductions are associated with tumor size changes after dendritic cell vaccination. Materials and Methods:The institutional animal care and use committee approved this study. Panc02 cells were implanted into the flanks of 27 C57BL/6 mice bilaterally. After tumors reached 10 mm, cell viability was evaluated, and iron-labeled dendritic cell vaccines were injected into the left hind footpad. The mice were randomly separated into the following three groups (n = 9 in each): Group 1 was injected with 1 million iron-labeled dendritic cells; group 2, with 2 million cells; and control mice, with 200 mL of phosphate-buffered saline. T1-and T2-weighted MR imaging of labeled dendritic cell migration to draining LNs was performed before cell injection and 6 and 24 hours after injection. The signal-to-noise ratio (SNR) of the draining LNs was measured. One-way analysis of variance (ANOVA) was used to compare Prussian blue-positive dendritic cell measurements in LNs. Repeated-measures ANOVA was used to compare in vivo T2-weighted SNR LN measurements between groups over the observation time points. Results:Trypan blue assays showed no significant difference in mean viability indexes (unlabeled vs labeled dendritic cells, 4.32% 6 0.69 [standard deviation] vs 4.83% 6 0.76; P = .385). Thirty-five days after injection, the mean left and right flank tumor sizes, respectively, were 112.7 mm 2 6 16.4 and 109 mm 2 6 24.3 for the 1-million dendritic cell group, 92.2 mm 2 6 9.9 and 90.4 mm 2 6 12.8 for the 2-million dendritic cell group, and 193.7 mm 2 6 20.9 and 189.4 mm 2 6 17.8 for the control group (P = .0001 for control group vs 1-million cell group; P = .00007 for control group vs 2-million cell group). There was a correlation between postinjection T2-weighted SNR decreases in the left popliteal LN 24 hours after injection and size changes at follow-up for tumors in both flanks (R = 0.81 and R = 0.76 for left and right tumors, respectively). Conclusion:MR imaging approaches can be used for quantitative measurement of accumulated iron-labeled dendritic cellbased vaccines in draining LNs. The amount of dendritic cell-based vaccine in draining LNs correlates well with observed protective effects.q RSNA, 2014

show abstract

Enhancement of antitumor immunity of dendritic cells pulsed with heat-treated tumor lysate in murine pancreatic cancer

Cited by 37 publications

References 25 publications

Chemo-immunotherapy mediates durable cure of orthotopic Kras^G12D/p53^−/−pancreatic ductal adenocarcinoma

Chemo-immunotherapy mediates durable cure of orthotopic Kras^G12D/p53^−/−pancreatic ductal adenocarcinoma

Establishment of an orthotopic pancreatic cancer mouse model: Cells suspended and injected in Matrigel

Antigen-loaded Dendritic Cell Migration: MR Imaging in a Pancreatic Carcinoma Model

Contact Info

Product

Resources

About

Enhancement of antitumor immunity of dendritic cells pulsed with heat-treated tumor lysate in murine pancreatic cancer

Cited by 37 publications

References 25 publications

Chemo-immunotherapy mediates durable cure of orthotopic KrasG12D/p53−/−pancreatic ductal adenocarcinoma

Chemo-immunotherapy mediates durable cure of orthotopic KrasG12D/p53−/−pancreatic ductal adenocarcinoma

Establishment of an orthotopic pancreatic cancer mouse model: Cells suspended and injected in Matrigel

Antigen-loaded Dendritic Cell Migration: MR Imaging in a Pancreatic Carcinoma Model

Contact Info

Product

Resources

About

Chemo-immunotherapy mediates durable cure of orthotopic Kras^G12D/p53^−/−pancreatic ductal adenocarcinoma

Chemo-immunotherapy mediates durable cure of orthotopic Kras^G12D/p53^−/−pancreatic ductal adenocarcinoma