Compositions having anti-fugetactic properties for treatment of cancer
A composition and cancer technology, applied in the directions of drug combinations, cancer antigen components, organic active components, etc., can solve the problem of unpredictable effective concentration of anti-removal agents
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Embodiment 1
[0187] Embodiment 1: Determining that the anti-trapping amount of AMD3100 is more than the going-up clipping amount
[0188] Freshly prepared and purified human CD3 from healthy donor peripheral blood + T cells. 20,000 T cells were loaded into the upper chamber of the Transwell in control, chemotaxis or xenotaxis settings (AMD3100 concentrations ranging from 0.1 μM to 10 μM). Migrated cells were counted in the lower chamber and quantified as previously described. Vianello et al. The Journal of Immunology, 2006, 176:2902-2914; Righi et al., Cancer Res.; 71(16); 5522-34, each of which is incorporated herein in its entirety.
[0189] We saw binary or bimodal chemotaxis of human CD3+ T cells towards AMD3100 ( figure 1 ; CI 2.3, at 1 μM) and expulsion ( figure 2 ; CI = 1.6 at 0.1 [mu]M) clear evidence of response (where a CI or chemotaxis index of 1.0 is the control). All wells were performed in triplicate.
Embodiment 2
[0190] Embodiment 2: Determine the local anti-removal amount of AMD3100
[0191] For quantitative migration assays, purified human CD3 + T cells (about 2×10 4 cells) added to each well In the upper chamber of the insert, to a total volume of 150 μl of Iscove's modified medium. Tumor cells (isolated from mammalian tumors) in DMEM containing 0.5% FCS were added to the lower, upper, or both lower and upper chambers of the Transwell to generate a standard "checkerboard" assay of cell migration, including Chemotaxis, removal and motility.
[0192] To determine the anti-removal concentration of AMD3100, T cells were incubated with 0.01 μΜ to 10 mMA AMD3100 before adding to the chamber.
[0193] Cells were harvested from the lower chamber after 3 hours and counted using a hemocytometer.
[0194] It is expected that T cells pre-incubated with certain concentrations of AMD3100 will exhibit a bimodal effect, with anti-attractive effects observed at lower concentrations and cytotox...
Embodiment 3
[0195] Example 3: Treatment of Prostate Cancer with Sipuleucel-T and Removal Agents
[0196] Antigen-presenting cells (APCs) were isolated from a 65-year-old patient with prostate cancer, exposed to PAP antigen and matured with GM-CSF. The APCs are administered to the patient. Over time, APCs stimulate specific T cell responses against the PAP antigen. When a T cell response is detected, a PBMC population is obtained from the patient's blood, mixed with AMD3100 and incubated. By infusion directly into the tumor, the patient received 1.6×10 7 A modified cell / AMD3100 composition. Alternatively, the cells and AMD310 can be administered separately and substantially simultaneously. It is contemplated that treatment with modified cells and AMD3100 will have a synergistic effect such that co-treatment results in reduced prostate cancer progression.
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