Utilization of Alternative Fibres Manufactured from Recycled PET Bottles in Concrete Technology for the Improvement of Fire Resistance.

This article addresses the potential use of secondary polymer fibres in the field of structural concrete as a replacement for primary polymer fibres (mainly polypropylene/PP/), which are used in concrete to enhance its resistance when exposed to high temperatures (especially in the case of fire). Research has shown that, in addition to PP fibres, polyethylene terephthalate/PET/fibres, produced by recycling packaging materials (mainly PET bottles), can also be used as an alternative. These fibres are industrially produced in similar dimensions as PP fibres and exhibit similar behaviour when added to fresh and hardened concrete.

Tumor growth accelerated by chemotherapy-induced senescent cells is suppressed by treatment with IL-12 producing cellular vaccines.

Standard-of-care chemo- or radio-therapy can induce, besides tumor cell death, also tumor cell senescence. While senescence is considered to be a principal barrier against tumorigenesis, senescent cells can survive in the organism for protracted periods of time and they can promote tumor development. Based on this emerging concept, we hypothesized that elimination of such potentially cancer-promoting senescent cells could offer a therapeutic benefit.

Administration of anti-CD25 mAb leads to impaired α-galactosylceramide-mediated induction of IFN-γ production in a murine model.

CD4(+)CD25(+)Foxp3(+) T regulatory cells (Tregs) and CD1d-restricted invariant natural killer T (iNKT) cells are two cell types that are known to regulate immune reactions. Depletion or inactivation of Tregs using specific anti-CD25 antibodies in combination with immunostimulation is an attractive modality especially in anti-tumour immunotherapy. However, CD25 is not expressed exclusively on Tregs but also on subpopulations of activated lymphocytes.

Genetically modified tumour vaccines producing IL-12 augment chemotherapy of HPV16-associated tumours with gemcitabine.

Genetically modified tumour cells producing cytokines such as interleukin 12 (IL-12) are potent activators of the antitumour immune responses and represent a promising therapeutic modality when combined with chemotherapy. The objective of this study was to examine whether IL-12-producing cellular vaccines can augment chemotherapy of human papilloma virus (HPV) 16-associated murine tumours with the cytostatic agent gemcitabine (GEM). We found that peritumoral administration of IL-12-producing tumour vaccines enhanced the effect of cytoreductive therapy with GEM both in non-metastasizing murine carcinoma TC-1 and in metastasizing murine carcinoma MK16.

NK1.1+ cells are important for the development of protective immunity against MHC I-deficient, HPV16-associated tumours.

Loss or downregulation of MHC class I molecules on tumour cells is a common mechanism by which tumours can escape T-cell mediated immune responses. In this study, we examined the role of different immune cell lineages in the development of immunity against tumours of the same aetiology but with different MHC class I expression. In vivo depletion of CD8+ cells, but not of CD4+ or NK1.

Induction of protective immunity against MHC class I-deficient, HPV16-associated tumours with peptide and dendritic cell-based vaccines.

Downregulation of MHC class I expression on the cell surface is a common mechanism by which tumour cells, including cervical carcinoma, can escape the T cell-mediated anti-tumour immunity. This downregulation represents an obstacle for the efficacy of anti-tumour vaccines. In this study, we investigated the efficacy of prophylactic peptide and peptide-pulsed dendritic cell-based vaccines in a murine model of experimental MHC class I-deficient tumours (TC-1/A9), expressing E6/E7 oncogenes derived from HPV16, and compared the efficacy of particular vaccination settings to anti-tumour protection against parental MHC class I-positive TC-1 tumours.

Therapy for minimal residual tumor disease: beta-galactosylceramide inhibits the growth of recurrent HPV16-associated neoplasms after surgery and chemotherapy.

Natural killer T (NKT) cells are potent modulators of antitumor immunity. Their protective effects can be achieved upon their activation by glycolipid ligands presented in the context of the CD1d molecule. These CD1d-binding glycolipid antigens have been described as potent therapeutic agents against tumors, infections, as well as autoimmune diseases.

HPV 16-associated tumours: IL-12 can repair the absence of cytotoxic and proliferative responses of tumour infiltrating cells after chemotherapy.

We have examined the effect of IL-12-producing cellular vaccines on the cytotoxicity and proliferative potential of CD45+ tumour-infiltrating cells (TIL) in mice carrying syngeneic TC-1 and TC-1/A9 HPV 16-associated tumours after chemotherapy with CBM-4A ifosfamide derivative. The chemotherapy resulted in the decrease of the CD4+ and CD8+ TIL, increase of the Gr-1+/CD11b+ TIL, no changes in the infiltration with CD4+/CD25+ Treg TIL, and decrease of the cytolytic and proliferative potential of the CD45+ TIL. Subsequent immunotherapy with the IL-12-producing, genetically modified TC-1 (TC-1-IL-12) cells increased tumour infiltration with CD8+ and CD4+ cells, decreased the Gr-1+/CD11b+ cells, and increased the cytolytic and proliferative potential of the CD45+ TIL.

IL-12 immunotherapy of minimal residual disease in murine models of HPV16-associated tumours: induction of immune responses, cytokine production and kinetics of immune cell subsets.

We have established animal models of HPV16-associated tumours with distinct levels of MHC class I expression. This model was used for examination of immune responses, production of cytokines and kinetics of immune cell subsets after IL-12 therapy of minimal residual tumour disease induced by CBA-4A (cyclophosphamide derivative) treatment. Upregulation of cytokine production was detected, compared to control animals without tumours.

Induction of MHC class I molecule cell surface expression and epigenetic activation of antigen-processing machinery components in a murine model for human papilloma virus 16-associated tumours.

Epigenetic events play an important role in tumour progression and also contribute to escape of the tumour from immune surveillance. In this study, we investigated the up-regulation of major histocompatibility complex (MHC) class I surface expression on tumour cells by epigenetic mechanisms using a murine tumour cell line expressing human E6 and E7 human papilloma virus 16 (HPV16) oncogenes and deficient in MHC class I expression, as a result of impaired antigen-presenting machinery (APM). Treatment of the cells with the histone deacetylase inhibitor Trichostatin A, either alone or in combination with the DNA demethylating agent 5-azacytidine, induced surface re-expression of MHC class I molecules.

CpG oligodeoxynucleotides are effective in therapy of minimal residual tumour disease after chemotherapy or surgery in a murine model of MHC class I-deficient, HPV16-associated tumours.

Oligodeoxynucleotides containing guanine-cytidine dimers (CpG ODN) are potent inducers of anti-tumour immune responses. In this study, we analyzed the capacity of CpG ODN to inhibit the growth of both MHC class I-positive and -deficient tumours after debulking the tumour mass by chemotherapy or surgery. We employed an animal model resembling human papillomavirus (HPV) 16-associated tumours.

Immunization with MHC class I-negative but not -positive HPV16-associated tumour cells inhibits growth of MHC class I-negative tumours.

Loss or downregulation of MHC class I molecules on tumour cells is a common mechanism by which tumours can escape from T-cell mediated immune responses. In this study we have investigated the immunologic crossreactivity between murine tumour cell lines expressing human papilloma virus (HPV) 16-derived E6/E7 oncoproteins with distinct surface expression of MHC class I molecules. The aims of this study were to demonstrate whether immune responses capable of coping with MHC class I-positive tumours can also be effective against their MHC class I-deficient derivatives and whether it is possible to induce immunity against MHC class I-deficient tumours by cellular vaccines based on MHC class I-deficient tumour cell lines.

Depletion of T(reg) cells inhibits minimal residual disease after surgery of HPV16-associated tumours.

It is generally accepted that T regulatory cells (T(reg) CD4(+)CD25(+)Foxp3(+)) play an important role in the suppression of tumour immunity. We examined the impact of T(reg) cell depletion with anti-CD25 antibody as adjuvant therapy in the treatment of minimal residual disease after excision of murine HPV16-associated tumours. We found that the depletion of T(reg) cells inhibited growth of the recurrences after surgery of HPV16-associated MHC class I+ as well as MHC class I-deficient tumours transplanted in syngeneic mice.

Inhibitory effects of unmethylated CpG oligodeoxynucleotides on MHC class I-deficient and -proficient HPV16-associated tumours.

Unmethylated oligodeoxynucleotides containing guanine-cytidine dimers (CpG ODN) have been described as potent inducers of selected antitumour immune responses and the immunotherapeutic efficacy of CpG ODN has been examined either alone or as a vaccine adjuvant. We hypothesized that CpG ODN therapy could be an effective tool for immunotherapy of not only conventional MHC class I(+) tumours but also of those tumours that have lost MHC class I expression during their progression. To address this hypothesis, we employed the animal model resembling MHC class I-proficient and -deficient human papilloma virus (HPV) 16-associated tumours.

Minimal residual disease as the target for immunotherapy and gene therapy of cancer (review).

Local recurrences at the site of tumour resection as well as distant micrometastases manifested after surgery represent major problems in oncology. Adjuvant immunotherapy and gene therapy may help to cope, at least partially, with these problems. Adjuvant modalities may be more effective in treating residual tumour disease compared to bulky tumours, owing to a favourable effector/target cell ratio.

Immune escape phenotype of HPV16-associated tumours: MHC class I expression changes during progression and therapy.

Malignant transformation of somatic cells followed by selection of the transformed cell populations can give rise to tumours that display an immune escape phenotype, MHC class I deficient neoplasms. Experiments were designed to examine whether the immune escape phenotype of HPV16-associated tumours is stable or whether the MHC class I expression can change during tumour progression and therapy. It has been found that temporary growth of MHC class I- tumour MK16/1/IIIABC in syngeneic mice can lead to up-regulation of the low MHC class I expression, both in the subcutaneous tumour inocula and in their lung metastases.

HPV16-associated tumours: therapy of surgical minimal residual disease with dendritic cell-based vaccines.

Dendritic cell (DC)-based vaccines are being intensively investigated for the treatment of a variety of human neoplasms. However, little attention has until now been paid to the use of DC-based vaccines for immunotherapy of tumour residua after surgery. In this communication, an animal model mimicking human HPV16-associated neoplasms was employed to examine the effect of DC-based vaccines for the treatment of surgical minimal residual tumour disease.

MHC class I down-regulation: tumour escape from immune surveillance? (review).

Malignant conversion and subsequent in vivo selection can give rise to the cell populations that show stable expression of an immune escape phenotype, MHC class I deficient neoplasms. Deficiencies associated with the MHC class I down-regulation are either irreversible, such as beta2 microglobulin and class I heavy chain gene disabling mutations, or reversible. The reversible MHC class I deficiencies involve all levels of the MHC class I-restricted antigen presentation machinery.

Treatment of minimal residual disease after surgery or chemotherapy in mice carrying HPV16-associated tumours: Cytokine and gene therapy with IL-2 and GM-CSF.

Moderately immunogenic HPV16-associated tumours TC-1 (MHC class I+, HPV16 E6/E7+, G12V Ha-ras+) and MK16/1/IIIABC (MK16, MHC class I-, HPV16 E6/E7+, G12V Ha-ras+), both of the H-2b haplotype and transplanted in syngeneic mice, were used to examine the effects of local IL-2 and GM-CSF cytokine or gene therapy in the treatment of minimal residual tumour disease. The mice carrying MHC class I+ TC-1 tumour residua after surgery were injected into the site of the surgery either with irradiated, IL-2 gene-modified MK16 tumour cells, or with recombinant IL-2. It has been found that both, the recombinant IL-2 and the IL-2 gene-modified tumour vaccine substantially reduced the percentage of tumour recurrences in the operated mice.

Tumour MHC class I downregulation and immunotherapy (Review).

MHC class I downregulation is an important mechanism of tumour escape from T cell-mediated immune responses. Approximately 40-90% of human tumours derived from various MHC class I+ tissues were reported to be MHC class I deficient. Decreased or absent MHC class I expression is frequently associated with the invasive and metastatic tumour phenotype.

Chemoimmunotherapy in mice carrying HPV16-associated, MHC class I+ and class I- tumours: Effects of CBM-4A potentiated with IL-2, IL-12, GM-CSF and genetically modified tumour vaccines.

The effectiveness of chemoimmunotherapy with ifosfamide derivative CBM-4A and recombinant IL-2, IL-12, GM-CSF, or genetically modified, cytokine-producing tumour vaccines was examined in mice carrying HPV16-associated, MHC class I+ (TC-1), and MHC class I- (MK16) tumours. Intraperitoneal treatment of TC-1 or MK16 tumour-bearing mice with CBM-4A produced a significant tumour-inhibitory effect. When the i.

Interleukin-2 and dendritic cells as adjuvants for surgical therapy of tumours associated with human papillomavirus type 16.

Moderately immunogenic HPV 16-associated tumours TC-1 (MHC class I(+), HPV 16 E6/E7(+), G12V Ha-ras(+)) and MK16/1/III ABC (MHC class I(-), HPV 16 E6/E7(+), G12V Ha-ras(+)), both of the H-2(b) haplotype and transplanted in syngeneic mice, were used to examine the adjuvant effects of IL-2 and dendritic cells for surgical therapy. Mice were inoculated s.c.

Tumour-inhibitory and antimetastatic effects of IL-2 in mice carrying MHC class I- tumours of HPV16 origin.

Oncogenic, moderately immunogenic, MHC class I- and class II-, B7-, MK16/1/III ABC (MK16) cells were previously established by co-transfection of HPV16 E6/E7 and activated H-ras oncogene DNA into C57BL/6 kidney cells. Subcutaneous transplantation of these cells produced progressively growing local neoplasms which metastasized spontaneously to lungs and lymph nodes. The MK16 cells were implanted into syngeneic mice and used to examine whether the tumour lacking the signal molecules required for the induction of and sensitivity to T cell immunity is susceptible to local IL-2 treatment and IL-2 gene therapy.