Dendritic cell vaccine transduced with ubiquitin-mesothelin fusion gene for pancreatic cancer

Pancreatology ◽  
2016 ◽  
Vol 16 (4) ◽  
pp. S171
Author(s):  
Motoki Miyazawa ◽  
Toshiyasu Ojima ◽  
Masahiro Katsuda ◽  
Manabu Kawai ◽  
Seiko Hirono ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Dendritic Cell ◽  
Fusion Gene ◽  
Dendritic Cell Vaccine ◽  
Cell Vaccine

Dendritic cell vaccine transduced with ubiquitin-mesothelin fusion gene for pancreatic cancer.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e14586-e14586
Author(s):  
Motoki Miyazawa ◽  
Toshiyasu Ojima ◽  
Masahiro Katsuda ◽  
Masaki Nakamura ◽  
Keiji Hayata ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Dendritic Cell ◽  
Fusion Gene ◽  
Dendritic Cell Vaccine ◽  
Cell Vaccine

scholarly journals A Double-blind Randomized Comparative Clinical Trial to Evaluate the Safety and Efficacy of Dendritic Cell Vaccine Loaded with WT1 Peptides (TLP0-001) in Combination with S-1 in Patients with Advanced Pancreatic Cancer Refractory to Standard Chemotherapy

2019 ◽  
Author(s):  
Masahiro Katsuda ◽  
Motoki Miyazawa ◽  
Toshiyasu Ojima ◽  
Akio Katanuma ◽  
Kenichi Hakamada ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Dendritic Cell ◽  
Advanced Pancreatic Cancer ◽  
Dendritic Cell Vaccine ◽  
Cell Vaccine ◽  
Standard Chemotherapy ◽  
Investigational Product ◽  
Double Blind ◽  
Safety And Efficacy

Abstract Background: Pancreatic cancer is a refractory malignancy and the development of a new effective treatment strategy is needed. We generated a dendritic cell vaccine by culturing monocytes obtained by apheresis of blood from each patient, inducing their differentiation into dendritic cells, and pulsing with tumor antigen peptides. However, the clinical efficacy of the vaccine has not been established. We therefore decided to conduct an exploratory clinical trial of dendritic cell vaccine loaded with Wilms’ tumor gene 1 peptides (TLP0-001) as a potential new treatment for patients with advanced pancreatic cancer refractory to standard chemotherapy. Methods: This is an investigator-initiated double-blind comparative trial. The patients were allocated to two groups in a 1:1 ratio through a central registration by dynamic allocation. A total of 185 patients with inoperable or metastatic pancreatic cancer who were refractory or intolerant to standard primary chemotherapy with gemcitabine plus nab-paclitaxel will be allocated to secondary treatment either with placebo in combination with S-1 (the control group) or TLP0-001 in combination with S-1 (the investigational product group). The primary objective of this trial is to evaluate the safety and efficacy (as measured by overall survival) of the investigational product by comparing the two groups. This clinical trial will be performed in accordance with Japanese Good Clinical Practice guidelines. Discussion: Clinical trials of the standard regimen, including gemcitabine, for advanced pancreatic cancer are ongoing worldwide. However, a strategy for after the primary treatment has not been established. We therefore decided to conduct this study to evaluate the safety and efficacy of TLP0-001 as a secondary treatment for pancreatic cancer in anticipation of the approval of this new drug in Japan. This trial is conducted with full consideration of safety as it is the first-in-human clinical trial of TLP0-001; thus, the trial will be conducted only at the Second Department of Surgery at Wakayama Medical University until the safety is confirmed by interim analysis. We plan to conduct a multicenter trial at 18 institutions in Japan after confirmation of the safety.

Combination therapy of dendritic cell vaccination plus chemotherapy in pancreatic cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15748-e15748
Author(s):  
Maurizio Chiriva-Internati ◽  
Leonardo Mirandola ◽  
Robert Bresalier ◽  
Scott Dahlbeck ◽  
Jose A. Figueroa ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Dendritic Cell ◽  
Locally Advanced ◽  
Vaccine Trial ◽  
Dendritic Cell Vaccine ◽  
Tumor Burden ◽  
Cell Vaccine ◽  
Dendritic Cell Vaccination ◽  
Synergistic Activity

e15748 Background: Pancreatic cancer is one of the world’s deadliest malignancies with an average 5-year survival rate of only 9%. Fortunately, immunotherapy is providing encouraging results for treatment of this historically resistant malignancy. Kiromic Biopharma is performing a phase I/II dendritic cell vaccine trial for progressive solid malignancies. We present here a notable response to metastatic pancreatic cancer. Methods: The patient is a 73-year-old male with the history of a locally advanced pancreatic cancer treated initially with gemcitabine, concurrent 5FU and radiation therapy, and consolidation 5FU, followed by surgical resection in 2009 . Although the patient did well exceeding typical survival curves, the patient’s cancer became metastatic, requiring multiple lines of chemotherapy including FOLFIRINOX, gemzar and abraxane, and most recently Onivyde and leucovorin/5FU in February - August, 2017 for progressive liver and lung metastases. The patient was then enrolled onto Kiromic Biopharma’s DC vaccination trial in March, 2018. Results: He subsequently received 6 ID autologous dendritic cell vaccinations over 12 weeks, demonstrating a tumor antigen specific immunogenic response by IFN-gamma immunoassay. Total tumor burden (TTB) prior to clinical trial enrollment at the sites of metastatic disease was 2,221mm2, and after completion of the DC vaccination protocol in May, 2018, the TTB increased to 4,466mm2 in June, 2018 (not considered to be pseudo-progression due to a corresponding increase in tumor biomarkers). The patient then received a repeat course of Onivyde and leucovorin/5FU on 8-3-18, completing that course of therapy on 9-14-18, with subsequent TTB decreasing to 2,986 mm2. Conclusions: The sequential combination of dendritic cell vaccine and chemotherapy resulted in a substantial response with a recession in metastatic tumor burden. A CT scan was obtained just 6 days after the 5 week course of Onivyde was completed, and given the optimal immunotherapy window after the DC vaccination, and the repeat of the same chemotherapy regimen, it is unlikely that chemotherapy alone led to such a rapid decrease in the TTB. Metastatic sites were likely populated by chemo resistant clones that survived the August 2017 administration of the Onivyde regimen. Thus, chemo alone would be unlikely to act so quickly. We hypothesize that there was synergistic activity between the DC immunotherapy and the Onivyde/5FU regimen, accounting for the decrease in TTB between May and September, 2018. Clinical trial information: NCT02705703.

scholarly journals A Double-blind Randomized Comparative Clinical Trial to Evaluate the Safety and Efficacy of Dendritic Cell Vaccine Loaded with WT1 Peptides (TLP0-001) in Combination with S-1 in Patients with Advanced Pancreatic Cancer Refractory to Standard Chemotherapy

2019 ◽  
Author(s):  
Masahiro Katsuda ◽  
Motoki Miyazawa ◽  
Toshiyasu Ojima ◽  
Akio Katanuma ◽  
Kenichi Hakamada ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Dendritic Cell ◽  
Advanced Pancreatic Cancer ◽  
Dendritic Cell Vaccine ◽  
Cell Vaccine ◽  
Standard Chemotherapy ◽  
Investigational Product ◽  
Double Blind ◽  
Safety And Efficacy

Abstract Background: Pancreatic cancer is a refractory malignancy and the development of a new effective treatment strategy is needed. We generated a dendritic cell vaccine by culturing monocytes obtained by apheresis of blood from each patient, inducing their differentiation into dendritic cells, and pulsing with tumor antigen peptides. However, the clinical efficacy of the vaccine has not been established. We therefore decided to conduct an exploratory clinical trial of dendritic cell vaccine loaded with Wilms’ tumor gene 1 peptides (TLP0-001) as a potential new treatment for patients with advanced pancreatic cancer refractory to standard chemotherapy. Methods: This is an investigator-initiated double-blind comparative trial. The patients were allocated to two groups in a 1:1 ratio through a central registration by dynamic allocation. A total of 185 patients with inoperable or metastatic pancreatic cancer who were refractory or intolerant to standard primary chemotherapy with gemcitabine plus nab-paclitaxel will be allocated to secondary treatment either with placebo in combination with S-1 (the control group) or TLP0-001 in combination with S-1 (the investigational product group). The primary objective of this trial is to evaluate the safety and efficacy (as measured by overall survival) of the investigational product by comparing the two groups. This clinical trial will be performed in accordance with Japanese Good Clinical Practice guidelines. Discussion: Clinical trials of the standard regimen, including gemcitabine, for advanced pancreatic cancer are ongoing worldwide. However, a strategy for after the primary treatment has not been established. We therefore decided to conduct this study to evaluate the safety and efficacy of TLP0-001 as a secondary treatment for pancreatic cancer in anticipation of the approval of this new drug in Japan. This trial is conducted with full consideration of safety as it is the first-in-human clinical trial of TLP0-001; thus, the trial will be conducted only at the Second Department of Surgery at Wakayama Medical University until the safety is confirmed by interim analysis. We plan to conduct a multicenter trial at 18 institutions in Japan after confirmation of the safety. Trial registration: University Hospital Medical Information Network Clinical Trials Registry, ID: UMIN000027179. Registered on 9 April 2017, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000031102

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