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To the editor,
With great interest have I read the recent contribution by Wintjens and colleagues providing a very thorough systematic review on drug delivery systems for the treatment of peritoneal carcinomatosis [1]—still one of the big challenges in oncology [2]. As complete as their review is, I would like to draw attention to another drug delivery system that is closely related to the topic where a prodrug, in this case ifosfamide, is converted in the peritoneal cavity by encapsulated cells expressing a P450 enzyme, CYP2B1. This converts ifosfamide in its active compound, 4-hydoxy-ifosfamide, that spontaneously decays to phosphoramide mustard and acrolein which alkylate DNA and protein, respectively. Using the standard model with GFP-expressing colon cancer cells as detailed in the excellent review [1] and also used by us with classical drug eluting beads[3, 4], we could demonstrate with the CYP2B1 encapsulated cells a significant tumor response all the way to complete remissions by using this gene directed enzyme prodrug therapy approach [5]. This concept, successfully proven in clinical studies in pancreatic cancer [6], could not be further developed due to manufacturing issues. Those, however, are resolved and further preclinical research in peritoneal carcinomatosis is ongoing.
References
Wintjens A, Simkens GA, Fransen PKH et al (2022) Intraperitoneal drug delivery systems releasing cytostatic agents to target gastro-intestinal peritoneal metastases in laboratory animals: a systematic review. Clin Exp Metastasis. https://doi.org/10.1007/s10585-022-10173-8
Abdel Mageed H, Van Der Speeten K, Sugarbaker P (2022) The many faces of intraperitoneal chemotherapy. Surg Oncol 40:101676
Yagublu V, Caliskan N, Lewis AL et al (2013) Treatment of experimental pancreatic cancer by doxorubicin-, mitoxantrone-, and irinotecan-drug eluting beads. Pancreatology 13:79–87
Keese M, Gasimova L, Schwenke K et al (2009) Doxorubicin and mitoxantrone drug eluting beads for the treatment of experimental peritoneal carcinomatosis in colorectal cancer. Int J Cancer 124:2701–2708
Samel S, Keese M, Lux A et al (2006) Peritoneal cancer treatment with CYP2B1 transfected, microencapsulated cells and ifosfamide. Cancer Gene Ther 13:65–73
Löhr M, Hoffmeyer A, Kroger J et al (2001) Microencapsulated cell-mediated treatment of inoperable pancreatic carcinoma. Lancet 357:1591–1592
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I am on the board of directors of PharmaCyte Biotech Inc., the company developing the CYP2B1 encapsulated cell therapy.
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Löhr, JM. Intraperitoneal drug delivery systems releasing cytostatic agents to target gastro‐intestinal peritoneal metastases in laboratory animals: a systematic review. Clin Exp Metastasis 39, 711 (2022). https://doi.org/10.1007/s10585-022-10181-8
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DOI: https://doi.org/10.1007/s10585-022-10181-8