Wyniki wyszukiwania

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A method for directly determining the number of dendritic cells and for evaluation of their function in small amounts of human peripheral blood

100%

Markowicz S., Skurzak H. M., Walewski J.

Archivum Immunologiae et Therapiae Experimentalis

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2001

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tom 49

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nr 1

2

Imatinib inhibits the renewal and tumorigenicity of CT-26 colon cancer cells after cytoreductive treatment with doxorubicin

64%

Przybyszewska M., Miloszewska J., Kotlarz A., Swoboda P., Pysniak K., Szczepek W., Kaczmarek L., Markowicz S.

Archivum Immunologiae et Therapiae Experimentalis

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2017

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tom 65

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nr 1

3

Nonviral transfection of human umbilical cord blood dendritic cells is feasible, but the yield of dentritic cells with transgene expression limits the application of this method in cancer immunotherapy

64%

Markowicz S., Niedzielska J., Kruszewski M., Oldak T., Gajkowska A., Machaj E. K., Skurzak H., Pojda Z.

Acta Biochimica Polonica

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2006

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tom 53

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nr 1

Dendritic cells (DC) generated from human umbilical cord blood might replace patients' DC in attempts to elicit tumor-specific immune response in cancer patients. We studied the efficiency of transfection of human cord blood DC with plasmid DNA carrying the enhanced version of green fluorescent protein (EGFP) as a reporter gene, to test if nonviral gene transfer would be a method to load DC with protein antigens for immunotherapy purposes. Cord blood mononuclear cells were cultured in serum-free medium in the presence of granulocyte-monocyte colony stimulating factor (GM-CSF), stem cell factor (SCF) and Flt-3 ligand (FL), to generate DC from their precursors, and thereafter transfected by electroporation. Maturation of DC was induced by stimulation with GM-CSF, SCF, FL and phorbol myristate acetate (PMA). Transfected DC strongly expressed EGFP, but transfection efficiency of DC, defined as HLA-DR+ cells lacking lineage-specific markers, did not exceed 2.5%. Expression of the reporter gene was also demonstrated in the DC generated from transfected, purified CD34+ cord blood cells, by stimulation with GM-CSF, SCF, FL, and tumor necrosis factor α (TNF-α). Transfection of CD34+ cells was very efficient, but proliferation of the transfected cells was much reduced as compared to the untransfected cells. Therefore, the yield of transgene-expressing DC was relatively low. In conclusion, nonviral transfection of cord blood DC proved feasible, but considering the requirements for immunotherapy in cancer patients, transfection of differentiated DC or generation of DC from transfected hematopoietic stem cells provide only a limited number of DC expressing the transgene.

4

Peptide-based cancer vaccines:adjuvant vaccination with melanoma peptide-pulsed dendritic cells (DCs) in stage III melanoma patients

52%

Markowicz S., Nowecki Z. I., Rutkowski P., Lipkowski A. W., Jakubowska-Mucka A., Biernacka M., Switaj T., Misicka A., Skurzak H., Polowiniak-Pracka H., Walewski J. A., Ruka W.

Acta Neurobiologiae Experimentalis

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2011

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tom 71

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nr 1

Background: This is a pilot study evaluating of high-risk melanoma patients (pts) treated with peptide-DC vaccine after lymphadenectomy (LND). DC vaccination was designed to induce the immune response against melanoma antigens in melanoma pts who remain at high risk of dissemination after LND. Methods: DCs were generated from the bone marrow cultured with GM-CSF, SCF, FLT3-L and TNF-a or from peripheral blood adherent monocytes cultured with GM-CSF and IL-4. DCs pulsed with HLA-A2-binding TYR, MART-1 and gp100 peptides and/or HLAA1-binding MAGE-1, MAGE-3 peptides, tumor lysate if available, or with tracer antigen keyhole limpet hemocyanin (KLH), were injected subcutaneously 9 times within 8 months (mos). Boost injections were performed after 12 and 24 mos. Vaccinated pts were matched to unvaccinated controls (22 of 869) by sex, number of metastatic lymph nodes, extracapsular involvement, completion or therapeutic LND, Breslow stage (T), ulceration, and lactate dehydrogenase (LDH) level prior to LND. Results: HLA-A2+, -A1+ or -A3+ melanoma pts (n=22), stage III, N1b-N3, enrolled between Sept. 2002 and Apr. 2004, received 5-16 vaccinations (median: 11) within 2 yrs. Cutaneous delayed type hypersensitivity (DTH) to melanoma peptides was induced in 12 of 22 pts. Peptide-specific IFN-g; producing CD8+ cells were detected in peripheral blood of 13 of 19 pts after vaccination. At least one of these responses to melanoma antigens was elicited in 17 of 22 pts. DTH to KLH was positive in 15 of 22 pts. Eight vaccinated pts are free of disease (follow up is 77-97 mos after LND), and 1 in progression is lost from follow-up by Aug 30, 2010. Survival analysis of vaccinated pts and matched controls is presented in Table 1. Conclusions: The DC/peptide vaccine elicited immune responses to melanoma antigens. Vaccinated pts had clinically substantially longer overall survival (OS) and disease free survival (DFS) than matched control. OS was associated with the immune responsiveness to melanoma antigens and to KLH. Table 1: Survival analysis of vaccinated pts and matched controls. Vaccinated pts (n=22) 3-year OS [%]: 68.2 Matched control (n=22) 3-year OS [%]: 25.7 p-value accounting for matching 0.0290 HR (95% CI)* 3.25 (1.06-9.97) Vaccinated pts (n=19**) 3-year DFS [%]: 40.9 Matched control (n=22) 3-year DFS [%]: 14.5 p-value accounting for matching 0.1083 HR (95% CI)* 2.16 (0.82-5.7) *Cox Proportional Model - Hazard Ratio (HR) of unvaccinated pts **3 pts with recurrence before LND were excluded.

5

Dendritic cell-based vaccination against tumor antigens for melanoma and lymphoma patients

39%

Markowicz S., Biernacka M., Switaj T., Lipkowski A. W., Misicka A., Nowecki Z., Polowniak-Pracka H., Ruka W., Rutkowski P., Sawadro-Rochowska M., Skurzak H., Kraszewska E., Zurawski Z., Rymkiewicz G., Borawska A., Federowicz I., Rozewska D., Szymczyk M., Jakubowska-Mucka A., Pojda Z., Walewski J.

Acta Biochimica Polonica

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2006

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tom 53

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nr Supplement 1

Ograniczanie wyników

A method for directly determining the number of dendritic cells and for evaluation of their function in small amounts of human peripheral blood

Imatinib inhibits the renewal and tumorigenicity of CT-26 colon cancer cells after cytoreductive treatment with doxorubicin

Nonviral transfection of human umbilical cord blood dendritic cells is feasible, but the yield of dentritic cells with transgene expression limits the application of this method in cancer immunotherapy

Peptide-based cancer vaccines:adjuvant vaccination with melanoma peptide-pulsed dendritic cells (DCs) in stage III melanoma patients

Dendritic cell-based vaccination against tumor antigens for melanoma and lymphoma patients