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1

Tumors and the danger model.

100%

Kowalczyk D. W.

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2002

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vol. 49

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issue 2

295-302

EN

This article reviews the evidence for the danger model in the context of immune response to tumors and the insufficiency of the immune system to eliminate tumor growth. Despite their potential immunogenicity tumors do not induce significant immune responses which could destroy malignant cells. According to the danger model, the immune surveillance system fails to detect tumor antigens because transformed cells do not send any danger signals which could activate dendritic cells and initiate an immune response. Instead, tumor cells or antigen presenting cells turn off the responding T cells and induce tolerance. The studies reviewed herein based on model tumor antigens, recombinant viral vectors and detection of tumor specific T cells by MHC/peptide tetramers underscore the critical role of tumor antigen presentation and the context in which it occurs. They indicate that antigen presentation only by activated but not by cancer or resting dendritic cells is necessary for the induction of immune responses to tumor antigens. It becomes apparent that the inability of dendritic cells to become activated provides a biological niche for tumor escape from immune destruction and seems to be a principal mechanism for the failure of tumor immune surveillance.

2

Cancer immunotherapy using cells modified with cytokine genes.

51%

Kowalczyk D. W., Wysocki P. J., Mackiewicz A.

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2003

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vol. 50

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issue 3

613-624

EN

The ability of various cytokines to hamper tumor growth or to induce anti-tumor immune response has resulted in their study as antitumor agents in gene therapy approaches. In this review we will concentrate on the costimulation of antitumor immune responses using modification of various cell types by cytokine genes. Several strategies have emerged such as (i) modification of tumor cells with cytokine genes ex vivo (whole tumor cell vaccines), (ii) ex vivo modification of other cell types for cytokine gene delivery, (iii) delivery of cytokine genes into tumor microenvironment in vivo, (iv) modification of dendritic cells with cytokine genes ex vivo. Originally single cytokine genes were used. Subsequently, multiple cytokine genes were applied simultaneously, or in combination with other factors such as chemokines, membrane bound co-stimulatory molecules, or tumor associated antigens. In this review we discuss these strategies and their use in cancer treatment as well as the promises and limitations of cytokine based cancer gene therapy. Clinical trials, including our own experience, employing the above strategies are discussed.

3

Expression of soluble recombinant TGF-β type II receptor fused with the Fc portion of human IgG1 (sTβRII-Fc) in NS0 cells

51%

Kwiatkowska E. P., Kazimierczak U., Mackiewicz A., Kowalczyk D. W.

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2006

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vol. 53

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issue 2

361-369

EN

We have constructed and expressed recombinant chimeric soluble TGF-β type II receptor fused with the Fc portion of human IgG1 (sTβRII-Fc) in NS0 mouse myeloma cells and isolated cell lines constitutively secreting very high levels of biologically active protein. The GS-NS0 expression system takes advantage of the strong human cytomegalovirus immediate early promoter expression vector and glutamine synthetase as a selectable marker. The recombinant chimeric receptor could be produced in high amounts and efficiently purified by one step chromatography on a protein A column. Biochemical studies revealed that recombinant sTβRII-Fc binds native TGF-β1 and TGF-β3 isoforms and neutralizes their activity in vitro.

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3 Acta Biochimica Polonica

1 2006

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3 Kowalczyk D. W.

2 Mackiewicz A.

1 Kazimierczak U.

1 Kwiatkowska E. P.

1 Wysocki P. J.

Tumors and the danger model.

Cancer immunotherapy using cells modified with cytokine genes.

Expression of soluble recombinant TGF-β type II receptor fused with the Fc portion of human IgG1 (sTβRII-Fc) in NS0 cells