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Extracorporeal photo-immunotherapy for circulating tumor cells.

ABSTRACT: It is well established that metastasis through the circulatory system is primarily caused by circulating tumor cells (CTCs). In this preliminary effort, we report an approach to eliminate circulating tumor cells from the blood stream by flowing the blood though an extracorporeal tube and applying photodynamic therapy (PDT). Chlorin e6 (Ce6), a photosensitizer, was conjugated to CD44 antibody in order to target PC-3, a prostate cancer cell line. PC-3 cells were successfully stained by the Ce6-CD44 antibody conjugate. PDT was performed on whole blood spiked with stained PC-3 cells. As the blood circulated through a thin transparent medical tube, it was exposed to light of 660 nm wavelength generated by an LED array. An exposure of two minutes was sufficient to achieve selective cancer cell necrosis. In comparison, to PDT of cells growing inside a tissue culture, the PDT on thin tube exhibited significantly enhanced efficiency in cell killing, by minimizing light attenuation by blood. It suggests a new extracorporeal methodology of PDT for treating CTCs as well as other hematological pathogens.

SUBMITTER: Kim G

PROVIDER: S-EPMC4444246 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Extracorporeal photo-immunotherapy for circulating tumor cells.

Kim Gwangseong G Gaitas Angelo A

PloS one 20150526 5

It is well established that metastasis through the circulatory system is primarily caused by circulating tumor cells (CTCs). In this preliminary effort, we report an approach to eliminate circulating tumor cells from the blood stream by flowing the blood though an extracorporeal tube and applying photodynamic therapy (PDT). Chlorin e6 (Ce6), a photosensitizer, was conjugated to CD44 antibody in order to target PC-3, a prostate cancer cell line. PC-3 cells were successfully stained by the Ce6-CD4 ...[more]

PMID: 26011055

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Project description:BackgroundPhoto(chemo)therapy is widely used to treat psoriasis, the pathogenesis of which might be caused by an imbalance of Th17 cells/regulatory T cells (Treg). In the present study, we evaluated the effects of photo(chemo)therapy on the Th17/Treg balance and Treg function.MethodsPeripheral blood was obtained from psoriasis patients treated with bath-psoralen ultraviolet A (UVA, n = 50) or narrowband ultraviolet B (UVB, n = 18), and age-matched healthy volunteers (n = 20). CD3(+)CD4(+)IL-17A(+) or CD4(+)CD25(+)Foxp3(+)cells were analyzed to estimate Th17 or Treg number by fluorescence-activated cell sorting. Moreover, CD4(+) CD25(-) T cells from patients treated with PUVA(n = 14) were incubated in CFSE and activated with or without CD4(+) CD25(+)T cells, and the suppressive function of CD4(+) CD25(+)T cells were analyzed.ResultsPhoto(chemo)therapy significantly reduced Th17 levels from 5.66 ± 3.15% to 2.96 ± 2.89% in patients with increased Th17 (Th17/CD4>3.01% [mean+SD of controls]). In contrast, photo(chemo)therapy significantly increased Treg levels from 2.77 ± 0.75 to 3.40 ± 1.88% in patients with less than 4.07% Treg level, defined as the mean of controls. Furthermore, while Treg suppressed the CD4(+)CD25(-) T cell proliferation to a greater extent in controls (Treg Functional Ratio 94.4 ± 4.28%) than in patients (70.3±25.1%), PUVA significantly increased Treg Functional Ratio to 88.1 ± 6.47%. Th17 levels in severe patients (>30 PASI) were significantly higher as compared to controls. Th17 levels that were left after treatment in the patients not achieving PASI 50 (3.78 ± 4.18%) were significantly higher than those in the patients achieving PASI 75 (1.83±1.87%). Treg levels in patients achieving PASI 90 (4.89 ± 1.70%) were significantly higher than those in the patients not achieving PASI 90 (3.90 ± 1.66%). Treg levels prior to treatment with Th17 high decreased group (5.16 ± 2.20%) was significantly higher than that with Th17 high increased group (3.33 ± 1.39%).ConclusionThese findings indicate that Treg is dysfunctional in psoriasis patients, and photochemotherapy restores those dysfunctional Treg. Photo(chemo)therapy resolved the Th17/Treg imbalance in patients with psoriasis.

Dataset Information

Extracorporeal photo-immunotherapy for circulating tumor cells.

Publications

Extracorporeal photo-immunotherapy for circulating tumor cells.

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