Other potentially treatable tumours

In animal models, encapsulated cytochrome P450 expressing cells have not only shown therapeutic effects against pancreatic and breast cancers but also against hepatocellular carcinoma, squamous carcinoma and peritoneal spread of gastrointestinal cancer [2]. Cells expressing more than one suicide gene (for example cytochrome P450 and CD), in combination with multiple pro-drugs, have been shown to be efficacious for the treatment in two mouse models of mammary cancer [5]. The results revealed that additive anti-tumour toxicity was found when both pro-drugs were given in both mouse models. This kind of multi-drug activating system can be expanded so that cells can be modified to express three -or- more pro-drug activating enzymes, opening up the possibility of tailoring treatment to individual patients by only applying the prodrugs to which the tumour responds.

Encapsulated cells activating a prodrug can also be successfully applied in combination with other, non-prodrug activating therapies such as low-dose radiation, cells producing anti-tumour monoclonal antibodies, agents that prevent neovasculariszation (required for tumour growth) and/or natural tumour growth inhibitors such as tumour necrosis factor [2].

Clearly, the use of encapsulated cells expressing suicide genes has great potential as the basis for the treatment of various forms of cancer. Proof-of-principle for this kind of anti-tumour approach has been demonstrated and will be extended to later stage clinical trials for pancreatic cancer and additional trials for the treatment of many other tumour types, eventually allowing multipronged approaches involving highly flexible patient/tumour specific treatment options with one or a limited number of encapsulated cell therapy products.
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References:
[1] Portsmouth D, Hlavaty J, Renner M (2007) Mol Aspects Med 28:4-41

[2] Salmons B, Brandtner EM, Hettrich K, Wagenknecht W, Volkert B, Fischer S, Dangerfield JA, Gunzburg WH (2010) Current Opinions in Molecular Therapy 12:450-460
[3] Salmons B, Hauser O, Gunzburg WH, Tabotta W (2007) BioProcessing Journal 4:36-43
[4] Löhr M, Hoffmeyer A, Kröger J, Freund M, Hain J, Holle A, Karle P, Knöfel WT, Liebe S, Müller P, Nizze H, et al (2001) Lancet 357:1591-1592
[5] Kammertöns T, Gelbmann W, Karle P, Salmons B, Günzburg WH, Uckert W (2000) Cancer Gene Therapy 7:629-63