7 research outputs found

    Near infra-red photoimmunotherapy with anti-CEA-IR700 results in extensive tumor lysis and a significant decrease in tumor burden in orthotopic mouse models of pancreatic cancer.

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    Photoimmunotherapy (PIT) of cancer utilizes tumor-specific monoclonal antibodies conjugated to a photosensitizer phthalocyanine dye IR700 which becomes cytotoxic upon irradiation with near infrared light. In this study, we aimed to evaluate the efficacy of PIT on human pancreatic cancer cells in vitro and in vivo in an orthotopic nude mouse model. The binding capacity of anti-CEA antibody to BxPC-3 human pancreatic cancer cells was determined by FACS analysis. An in vitro cytotoxicity assay was used to determine cell death following treatment with PIT. For in vivo determination of PIT efficacy, nude mice were orthotopically implanted with BxPC-3 pancreatic tumors expressing green fluorescent protein (GFP). After tumor engraftment, the mice were divided into two groups: (1) treatment with anti-CEA-IR700 + 690 nm laser and (2) treatment with 690 nm laser only. Anti-CEA-IR700 (100 μg) was administered to group (1) via tail vein injection 24 hours prior to therapy. Tumors were then surgically exposed and treated with phototherapy at an intensity of 150 mW/cm2 for 30 minutes. Whole body imaging was done subsequently for 5 weeks using an OV-100 small animal imaging system. Anti-CEA-IR700 antibody bound to the BxPC3 cells to a high degree as shown by FACS analysis. Anti-CEA-IR700 caused extensive cancer cell killing after light activation compared to control cells in cytotoxicity assays. In the orthotopic models of pancreatic cancer, the anti-CEA-IR700 group had significantly smaller tumors than the control after 5 weeks (p<0.001). There was no significant difference in the body weights of mice in the anti-CEA-IR700 and control groups indicating that PIT was well tolerated by the mice

    Light-induced cell death by cell-bound anti-CEA-IR700.

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    <p>BxPC-3 cells were incubated with anti-CEA-IR700 conjugate (10 μg/ml). Rapid cell killing was observed with a dose of 32 J/cm<sup>2</sup> of 690 nm near-infrared light (blue circles), whereas only little cell killing occurred without illumination (green triangles). Death in light-treated cells in the absence of anti-CEA-IR700 was negligible (data not shown).</p

    Staining of BxPC-3 cells with anti-CEA antibody and quantification of binding sites.

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    <p>BxPC-3 cells were treated with anti-CEA antibody and stained with a fluorochrome conjugated secondary antibody against anti-CEA (red, filled), or control-stained with secondary antibody only (black, open) and analyzed by flow cytometry. Gating was for the main population (A). The anti-CEA antibody binding capacity, determined with reference beads, was very high (2,227,000 binding sites per cell) (B).</p

    Resected tumors.

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    <p>The top panel shows the tumors from the control group and the bottom panel shows tumors from the treatment group.</p

    Graphical representation of tumor weights.

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    <p>A significant difference was noted with average tumor weights after tumor resection. A significant difference in tumor weight was noted between the treatment and control groups (p<0.001).</p
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