Cell therapy using microencapsulated 293 cells transfected with a gene construct expressing CYP2B1, an ifosfamide converting enzyme, instilled intra-arterially in patients with advanced-stage pancreatic carcinoma: a phase I/II study

Löhr, Matthias; Bago, Zoltan Tibor; Bergmeister, Helga; Ceijna, Manfred; Freund, Mathias; Gelbmann, Wolfgang; Günzburg, Walter H.; Jesnowski, Ralf; Hain, Johannes; Hauenstein, Karlheinz; Henninger, Wolfgang; Hoffmeyer, Anne; Karle, Peter; Kröger, Jürgen; Kundt, Günther; Liebe, Stefan; Losert, Udo; Müller, Petra; Probst, Alexander J.; Püschel, K; Renner, Matthias; Renz, Renate; Saller, Robert; Salmons, Brian; Schuh, Maximilian; Schwendenwein, Ilse; Rombs, Kerstin von; Wagner, Thomas; Walter, Ingrid

doi:10.1007/s001090050366

Cited by 53 publications

(28 citation statements)

References 17 publications

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“…Pre = Prior to investigation (angiography); OP = day of angiography (after the procedure). these results, a clinical protocol was started in patients with inoperable, advanced-stage pancreatic carcinoma [18], confirming the safety of this approach [19].…”

Section: Discussionmentioning

confidence: 71%

Intra-arterial instillation of microencapsulated, ifosfamide-activating cells in the pig pancreas for chemotherapeutic targeting

et al. 2003

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Section: Discussionmentioning

confidence: 71%

Intra-arterial instillation of microencapsulated, ifosfamide-activating cells in the pig pancreas for chemotherapeutic targeting

et al. 2003

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“…. In fact, NovaCaps®, the encapsulated cell therapy product based on this strategy, have been tested in a Phase I/II clinical trial in patients with pancreatic cancer and the results are promising [125].…”

Section: Applications Of Encapsulated Cells In Hydrogel For Cancer Thmentioning

confidence: 99%

Microfluidic-Based Synthesis of Hydrogel Particles for Cell Microencapsulation and Cell-Based Drug Delivery

2012

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Encapsulation of cells in hydrogel particles has been demonstrated as an effective approach to deliver therapeutic agents. The properties of hydrogel particles, such as the chemical composition, size, porosity, and number of cells per particle, affect cellular functions and consequently play important roles for the cell-based drug delivery. Microfluidics has shown unparalleled advantages for the synthesis of polymer particles and been utilized to produce hydrogel particles with a well-defined size, shape and morphology. Most importantly, during the encapsulation process, microfluidics can control the number of cells per particle and the overall encapsulation efficiency. Therefore, microfluidics is becoming the powerful approach for cell microencapsulation and construction of cell-based drug delivery systems. In this article, I summarize and discuss microfluidic approaches that have been developed recently for the synthesis of hydrogel particles and encapsulation of cells. I will start by classifying different types of hydrogel material, including natural biopolymers and synthetic polymers that are used for cell encapsulation, and then focus on the current status and challenges of microfluidic-based approaches. Finally, applications of cell-containing hydrogel particles for cell-based drug delivery, particularly for cancer therapy, are discussed.

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“…18 Fifty capsules containing 5 ϫ 10 5 5 CYP2B1 transfected cells were injected peritumorally 24 hr after radiation. Ifosfamide (50 mg/kg, Holoxan, Asta Medica, Germany) supplemented with 2-mercaptoethanesulphonate (MESNA, Asta Medica) was given intraperitoneally every 3 days.…”

Section: Therapy Regimenmentioning

confidence: 99%

Combined therapy of experimental pancreatic cancer with CYP2B1 producing cells: Low-dose ifosfamide and local tumor irradiation

et al. 2004

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Local therapy of pancreatic cancer with microencapsulated CYP2B1-producing cells and ifosfamide showed an effect both on the primary tumor and on distant metastatases. This possibly represents a consequence of the activation of immune response. Other studies have demonstrated that local tumor irradiation leads to the activation of the intratumoral lymphocyte infiltration. The aim of our study was to investigate the efficacy of the combined therapy with low-dose irradiation, ifosfamide and CYP2B1-producing cells. Syngenic pancreatic cancer was induced in 38 Lewis-rats by subcutaneous inoculation of 1 ؋ 10 6 (DSL6A) tumor cells. Microencapsulated CYP2B1-producing cells were injected peritumorally 10 --12 weeks after tumor implantation. Animals were randomized to the following groups: 1) control (NaCl, 1 ml i.p.), 2) ifosfamide (50 mg/kg, i.p., (3؋/week), 3) local irradiation with 5 Gy and 4) ifosfamide plus irradiation. The tumor growth was monitored for 3 weeks. The tumor infiltration with CD4؉, CD8؉, NK-cells, microvessel density and proliferation rates were investigated by immunohistochemistry. Cytokine plasma level for TNF-␣ were measured by ELISA. Seven of 9 animals in the group of combined therapy showed an objective response to the therapy. The therapy with ifosfamide or radiation alone showed 5 and 3 responders, respectively. The mean tumor volume was significantly reduced after combined ifosfamide plus radiation therapy in the first week, whereas monotherapy with ifosfamide or radiation significantly decreased tumor growth earliest after 2 and 3 weeks, respectively. The high plasma level of TNF-␣ in the control group was significantly reduced after combined ifosfamide/irradiation treatment. The lymphocyte infiltration and tumor proliferation were not significantly different between the groups. Microvascular density was significantly increased after ifosfamide and ifosfamide plus irradiation therapy. The combination of ifosfamide/CYP2B1-producing cells and irradiation showed an earlier therapeutical effect on the growth of rat pancreatic cancer than the irradiation or ifosfamide alone. There was no evidence of late activation of lymphocyte infiltration and PCNA-positive tumor cells.

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Cell therapy using microencapsulated 293 cells transfected with a gene construct expressing CYP2B1, an ifosfamide converting enzyme, instilled intra-arterially in patients with advanced-stage pancreatic carcinoma: a phase I/II study

Cited by 53 publications

References 17 publications

Intra-arterial instillation of microencapsulated, ifosfamide-activating cells in the pig pancreas for chemotherapeutic targeting

Intra-arterial instillation of microencapsulated, ifosfamide-activating cells in the pig pancreas for chemotherapeutic targeting

Microfluidic-Based Synthesis of Hydrogel Particles for Cell Microencapsulation and Cell-Based Drug Delivery

Combined therapy of experimental pancreatic cancer with CYP2B1 producing cells: Low-dose ifosfamide and local tumor irradiation

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