Phase I trial of preoperative intratumoral injection of immature dendritic cells and OK‐432 for resectable pancreatic cancer patients

Endo, Hisahito; Saito, Takuro; Kenjo, Akira; Hoshino, Mika; Terashima, Masanori; Sato, Tetsu; Anazawa, Takayuki; Kimura, Takashi; Tsuchiya, Takao; Irisawa, Atsushi; Ohira, Hiromasa; Hikichi, Takuto; Takagi, Tadayuki; Gotoh, Mitsukazu

doi:10.1007/s00534-011-0457-7

Cited by 49 publications

(42 citation statements)

References 32 publications

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“…70 A Phase I trial evaluating patients with nonmetastatic and resectable pancreatic adenocarcinoma compared EUS-FNI of DC plus OK-432 (an immune-potentiating agent) to 9 patients with a control group of 15 patients receiving standard chemotherapy. 71 There was no significant difference in median survival times, but FNI of DC with OK-432 was fairly well tolerated; however, two patients in the DC arm developed pancreatic fistula relative to one of 15 patients in control arm. This was not statistically significant.…”

Section: Dendritic Cell Immunotherapymentioning

confidence: 82%

Novel diagnostic and therapeutic modalities using endoscopic ultrasound in pancreatic disease

Luthra

Mishra

2017

Int J Gastrointest Interv

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Section: Dendritic Cell Immunotherapymentioning

confidence: 82%

Novel diagnostic and therapeutic modalities using endoscopic ultrasound in pancreatic disease

Luthra

Mishra

2017

Int J Gastrointest Interv

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“…The results were encouraging in five patients, but further studies are needed [117]. Immature dendritic cells and OK-432 were preoperatively injected intratumorally in nine patients with resectable pancreatic cancer; there were no complications, and survival was prolonged in only one patient with distant metastasis [115].…”

Section: Antitumor Therapymentioning

confidence: 97%

“…Vaccination with dendritic cells as immunotherapy is considered a potential anti-cancer tool, and OK-432 represents a maturation stimulus for dendritic cells [115]. One early trial used concomitant immunotherapy with EUS-guided injection of OK-432, followed by intravenous infusion of lymphokine-activated killer cells stimulated with anti-CD3 monoclonal antibody.…”

Section: Antitumor Therapymentioning

confidence: 99%

Endoscopic Ultrasound in Pancreatic Cancer: The New Perspective

Seicean¹

2014

Pancreatic Cancer - Insights Into Molecular Mechanisms and Novel Approaches to Early Detection and Treatment

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“…Different tumor antigens and protocols have been used in this DCs vaccination strategy, which has achieved activation of anti-tumor immune response, delayed tumor growth and improvement in survival, as shown in Table 2 [165][166][167][168][169][170][171][172][173][174][175][176][177][178][179][180][181][182][183][184].…”

Section: Dcs Based Vaccinesmentioning

confidence: 99%

Pancreatic Cancer Fostered Immunosuppression Privileges Tumor Growth and Progression

Basso¹

2014

J Clin Cell Immunol

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The high progression rate of Pancreatic Ductal Adenocarcinoma (PDAC) depends on intrinsic genetic and epigenetic cancer cell aberrations and a profound imbalance in immune system cells infiltrating the PDAC stroma. Direct or exosome mediated shedding in the tumor microenviroment of different molecules (e.g. cytokines, chemokines, lectins) causes tumor, pancreatic stellate and inflammatory cells to recruit numerous immunosuppressive cells in the PDAC microenvironment and inhibit immune effector cells. CD8 + T and dendritic immune effector cells (DCs) are reduced, while immunosuppressive T regulatory cells (T reg ), Myeloid Derived Suppressor Cells (MDSCs) and M2 Tumor Associated Macrophages (TAMs) accumulate in the PDAC stroma, mainly at the invasive front area. The imbalance in CD4 + T cell subsets, with Th2 and Th17 prevailing over the Th1 effector arm, is associated with a worse PDAC prognosis that depends on the failure of immune system cells to destroy cancer cells, and the accumulation of immune cells in the PDAC stroma can have pro-neoplastic and prometastatic effects. CD4 + T cells are indispensable for PDAC development; T reg and M2 polarized TAMs favor neoangiogenesis and the epithelial to mesenchymal transition of PDAC cells, a pre-requisite for metastases; MDSCs favor metastases by releasing pro-metastatic inflammatory mediators such as S100A8/A9 proteins, and by creating pre-metastatic niches (in metastatic sites). Of the several treatment strategies aiming to abolish the immune cell imbalance in PDAC, and targeting the immune system, DCs manipulation, vaccination with tumor derived antigens and T reg depletion appear to be of benefit, but still require validation before being recommended in the clinical setting.

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Phase I trial of preoperative intratumoral injection of immature dendritic cells and OK‐432 for resectable pancreatic cancer patients

Abstract: PEU-FNI was feasible and safe, and further study needs to confirm and enhance antitumor responses.

Cited by 49 publications

References 32 publications

Novel diagnostic and therapeutic modalities using endoscopic ultrasound in pancreatic disease

Novel diagnostic and therapeutic modalities using endoscopic ultrasound in pancreatic disease

Endoscopic Ultrasound in Pancreatic Cancer: The New Perspective

Pancreatic Cancer Fostered Immunosuppression Privileges Tumor Growth and Progression

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