Search results

1

In vitro co-stimulation of anti-tumor activity by soluble B7 molecules

100%

He W., Hu Z.-B., Liu F., Feng X.-Q., Zou P.

Acta Biochimica Polonica

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2006

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vol. 53

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issue 4

807-813

EN

In order to investigate the anti-tumor activity of a soluble B7-1/immunoglobulin G fusion protein and explore an effective method to eliminate immune escape of tumor cells, a recombinant vector encoding this fusion protein was constructed and constitutively expressed in Chinese hamster ovary cells. After purification with protein G affinity chromatography, the soluble fusion protein was tested for bioactivity. Results showed that the fusion protein could significantly increase the density of B7-1 molecules on WEHI-3 cells, a mouse leukemia cell line. Through allogeneic mixed lymphocyte tumor cultures, it was demonstrated that, with the presence of the first signal, it could also significantly enhance T cell activation and killing activity against WEHI-3 cells and interleukin-2 secretion by activated mouse T lymphocytes. The conclusion can be drawn that the soluble B7-IgG fusion protein has a potent capacity to generate or enhance anti-tumor immune response in vitro, and its clinical value deserves further investigation.

2

Ovarian cancer: early detection, angiogenesis, lymphangiogenesis and current prospects for therapy

100%

Wertel I., Bednarek W., Czekierdowski A., Kotarski J.

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issue 1

24-28

EN

I Chair and Department of Gynecological Oncology and Gynecology is a specialist research center providing help in diagnostics and treatment of gynecological malignancies. The research work is focused on the processes of angiogenesis and lymphangiogenesis. Development of blood and lymphatic vessels is subject to research in a wide range of malignancies, including ovarian cancer, endometrial cancer and uterine sarcomas. Angiogenesis in malignancies of the female genital tract is investigated by using some modern 3D sonography that uses high-definition blood flow imaging. Ovarian Tumors and Early Ovarian Cancer Detection unit was established in 2002 and since that time more than 3500 patients with difficult to diagnose tumors have been consulted and treated in the Department. Ovarian cancer immunology studies are the second leading research fiekld in the 1st Chair Department of Gynecological Oncology and Gynecology. The Department is well equipped with diagnostic devices as well as a scientific laboratory. This allows for studies in the fields of imaging of masses, their immunology, biochemistry and molecular biology. Understanding immunological response in patients with ovarian cancer is the key to develop new, effective therapies, including immunological vaccines. In this area we are cooperating with prominent international research centers: Department of Surgery, University of Michigan and Department of Microbiology and Immunology, University of Arkansas. Results of our research are published in both Polish and international journals specializing in fields of gynecology, oncology, immunology and basic science.

3

Diminished expression of ICOS, GITR and CTLA-4 at the mRNA level in T regulatory cells of children with newly diagnosed type 1 diabetes

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Łuczyński W., Wawrusiewicz-Kurylonek N., Stasiak-Barmuta A., Urban R., Iłendo E., Urban M., Hryszko M., Krętowski A., Górska M.

Acta Biochimica Polonica

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2009

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vol. 56

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issue 2

361-370

EN

Diabetes mellitus is one of the most common chronic diseases in children. T regulatory cells (Tregs) modulate response to autoantigens and probably play a role in pathogenesis of type 1 diabetes (T1DM). The aim of the present study was the assessment of T regulatory cells including their percentages and expression of critical genes in these cells in children with newly diagnosed type 1 diabetes. The examined group consisted of 50 children with T1DM. A flow cytometric analysis of T-cell subpopulations was performed using the following markers: anti-CD4, anti-CD25 and anti-CD127 (=IL-7R). Additionally, T regulatory cells were isolated for assessment of mRNA levels for chosen genes with the real-time RT-PCR technique. The percentages of CD4+CD25highCD127dim/- were very low and did not differ between T1DM and control children. We did not observe any statistically significant differences between healthy and diabetic children in mRNA expression for FoxP3, IL-7R (CD127), IL-8RA, IL-10RA, IL-12A, IL-2RA (CD25), IL-21, STAT1, STAT3, SOCS2, SOCS3, TGF-β1-R1, TGF-β-R2 and TBX-21 genes. Interestingly the mRNA level for CTLA-4, ICOS1, IL-23, IL-27, SMAD3 and GITR were lower in Treg cells of children with diabetes compared to the control patients. No disturbances in the percentages of T regulatory cells in patients with diabetes but diminished expression of some elements important in Treg function could be the result of an immunologic imbalance accompanying the onset of the diabetes. The results of our study should be used in future research in the field of immunotherapy in pediatric diabetes.

4

Evaluation of immature monocyte-derived dendritic cells generated from patients with colorectal cancer

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Maciejewski R., Radej S., Furmaga J., Chrościcki A., Rudzki S., Roliński J., Wallner G.

Polish Journal of Surgery

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2013

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vol. 85

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issue 12

714-720

EN

Dendritic cells are heterogeneous population of the leukocytes and most potent APC in activation of naive T lymphocytes. Therefore the DCs generated in vitro are under research for their application in anti-tumor immunotherapy. The aim of the study was generation of the immature dendritic cells from peripheral blood monocytes collected from colorectal cancer patients and comparison of their ability to endocytosis, cytokine production and immunophenotype to DCs generated from healthy donors. Material and methods. 16 adenocarcinoma stage II patients were included in the study. Dendritic cells were generated in the presence of rhGM-CSF and IL-4. PBMC were isolated from the blood of patients and 16 healthy donors - control group. Immunophenotype, ability of endocytosis of Dextran- FITC as well as intracellular IL-12 expression of the generated dendritic cells was measured using flow cytometry. The cytokines (IL-6, IL-10, IL-12p70, IFN-γ) concentration in the supernatants of DCs culture was measured by ELISA. Results. The percentage of the immature dendritic cells and expression of CD206 and CD209 antigens was significantly higher in patients group (p <0.05 and p <0.001 respectively). Significantly (p <0.001) higher expression of the antigens which initiate the Th2 immune response (CD80-/CD86 + and B7-H2 + / CD209 +) was in the patients group. There were no differences in endocytosis ability and the cytokines (IL-6, IL-10, IL-12p70, IFN-γ) concentration between investigated groups. Conclusions. High immature markers expression on the generated dendritic cells together with identical endocytosis ability in patients group is advantageous in antitumor autologous cells immunotherapy planning. However there is one troubling fact - high expression of markers, which may induce tolerance to particular antigen. It seems to be more reasonable to use the autologous DCs in the antitumor immunotherapy, especially due to the incompatibility in allogenic cells in the context of HLA complex.

5

Advanced skin melanoma – systemic treatment

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Kruczała M., Ziobro M., Grela-Wojewoda A., Cedrych I.

OncoReview

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2015

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vol. 5

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issue 3

A133-138

EN

In Poland, morbidity and mortality rates for melanoma are constantly increasing. In the case of inoperable disease or distant metastases, prognosis remains poor. For many years, dacarbazine has been the gold standard in systemic treatment. Recently, a significant progress in melanoma therapy has been observed. Introducing targeted therapy or immunotherapy significantly improved treatment outcomes. This review paper presents current knowledge on systemic treatment of advanced melanoma, including treatment availability in Poland.

6

First Polish Hand Allograft - 6-Month Report

100%

Jabłecki J., Kaczmarzyk L., Patrzałek D., Domanasiewicz A., Paruzel M., Chełmoński A., Kaczmarzyk J.

Polish Journal of Surgery

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2007

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vol. 79

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issue 3

232-238

EN

The transplant recipient is a 32 year-old man who lost his right, dominant upper limb on the level of the midpoint of his forearm in an accident 14 years ago. After a comprehensive pretransplantation evaluation and informed consent process he received a transplant of the right forearm, matched for size and skin tone, of a brain-dead man aged 47. The donor's limb was amputated at the elbow and irrigated with UW solution. We dissected the donor and recepient limbs simultaneously. Appropriate lengths of anatomical structures were matched. Bone fixation was performed with Rush pins, without bony transplants; the muscles were anastomosed in layers and the skin wound was closed without a skin transplant. The cold ischemia time was 10.5 hours. Immunosuppresion included simulect, tacrolimus, mycophenolic acid, and prednisone. Maintanance therapy included tacrolimus (15 ng/ml), mycophenolic acid, and encorton.There were no intraoperative or early postoperative complications. No episodes of rejection were observed. Immunosupression was well tolerated. The intensive physiotherapy led to satisfactory progress of motor function recovery. Reinnervation was excellent, and after 6 months, Tinel's sign was present over 40% of the respective lengths of the median and ulnar nerves. Follow-up included routine post-transplant laboratory tests, skin biopsies, bacteriological tests, and physiotherapy.

7

Partial remission in patient with Richter syndrome: an „emergency” treatment with pixantrone

88%

Szwedyk P.

OncoReview

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2020

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vol. 10

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issue 2

52-56

EN

Chronic lymphocytic leukemia is the most commonly recognized type of leukemia in adults. The appearance of systemic symptoms such as weight loss, fever, or local symptoms in the form of rapidly growing organomegaly, lymphadenopathy in a patient with CLL raises the suspicion of transformation into a high-grade lymphoma – defined as Richter syndrome which is usually associated with very poor prognosis. The described case concerns a 71-year-old patient with this diagnosis, in whom due to the confirmed resistance to subsequent lines of immuno- and chemotherapy, an „emergency” treatment with a modern chemotherapy drug from the aza-anthracendion group – pixantrone was used. Treatment with pixantrone was associated with a relatively good response, translating into partial remission (also in the area of infiltrative changes in the head and neck structures), stabilization of the course of the disease and, consequently, allowed to extend the patient’s life.

8

CD40 stimulation induces differentiation of acute lymphoblastic leukemia cells into dendritic cells

88%

Łuczyński W., Stasiak-Barmuta A., Iłendo E., Krawczuk-Rybak M., Malinowska I., Mitura-Lesiuk M., Parfieńczyk A., Szymański M.

Acta Biochimica Polonica

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2006

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vol. 53

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issue 2

377-382

EN

Despite the very high percentage of long-term remissions in acute lymphoblastic leukemia (ALL) in children, some of them suffer from recurrence of the disease. New treatment modalities, e.g. effective geno- and immunotherapy are needed. The use of neoplasmatic cells to present tumor antigens is one of the approaches in cancer vaccines. ALL cells lack the expression of costimulatory molecules and are poor antigen presenting cells (APCs) for T-cell activation. CD40/40L interaction stimulates B-cells to proliferate, differentiate, upregulate costimulatory molecules and increase antigen presentation. The aim of the study was to test the hypothesis that ALL cells can be turned into professional APCs by CD40L activation. Children with B-cell precursor ALL were enrolled into the study. Mononuclear cells from bone marrow or peripheral blood were stimulated with CD40L and interleukin 4. Results: 1) after culture we noted upregulation of all assessed costimulatory, adhesion and activatory molecules i.e. CD1a, CD11c, CD40, CD54, CD80, CD83, CD86, CD123, HLA class I and II; 2) CD40L activated ALL cells induced proliferation of allogeneic T-cells (measured by [3H]thymidine incorporation). These results confirm the possibility of enhancing the immunogenicity of ALL cells with the CD40L system and indicate that this approach can be used in immunotherapeutic trials.

9

Immunotherapy of head and neck squamous cell carcinoma (HNSCC). Immune checkpoint blockade

75%

Przybylski K., Majchrzak E., Weselik L., Golusiński W.

Otolaryngologia Polska

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2018

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vol. 72(6)

10-16

EN

Treating patients with squamous cell carcinoma of the head and neck is a significant problem. There is an increase in the incidence of malignant neoplasms in this region. Surgery, radiotherapy and chemotherapy are often not sufficient methods of treatment. Thorough analysis of processes occurring in the tumor microenvironment has allowed to distinguish three stages that make up the reaction of the human body to hostile antigens, which are tumor antigens. Understanding these mechanisms has resulted in the introduction of a new term immune-oncology. It is an area of cancer treatment that focuses on use of the patient’s immune system to combat the disease. Immunotherapy has had positive effects in cancer patients. The use of immune checkpoint inhibitors, such as anti-CTLA-4 and PD-1 monoclonal antibodies has enabled the modulation of T cell functions, consequently eliminating immunosuppression in the tumor microenvironment. Clinical trials were conducted using nivolumab and ipilimumab, which confirmed their clinical usefulness. The approval by FDA of nivolumab in treatment of recurrent and metastatic squamous cell carcinoma of the head and neck has increased the overall survival time of patients as well as disease free survival. Statistical data indicate an advantage of immunotherapy over other treatment methods at an advanced stage of cancer. This work aims to discuss basic issues related to immunotherapy, in particular immunotherapy in patients with squamous cell carcinoma of the head and neck.

10

Immunotherapy of head and neck squamous cell carcinoma (HNSCC). Immune checkpoint blockade

75%

Przybylski K., Majchrzak E., Weselik L., Golusiński W.

Polish Journal of Otolaryngology

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2018

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vol. 72

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issue 6

10-16

EN

Treating patients with squamous cell carcinoma of the head and neck is a significant problem. There is an increase in the incidence of malignant neoplasms in this region. Surgery, radiotherapy and chemotherapy are often not sufficient methods of treatment. Thorough analysis of processes occurring in the tumor microenvironment has allowed to distinguish three stages that make up the reaction of the human body to hostile antigens, which are tumor antigens. Understanding these mechanisms has resulted in the introduction of a new term immune-oncology. It is an area of cancer treatment that focuses on use of the patient’s immune system to combat the disease. Immunotherapy has had positive effects in cancer patients. The use of immune checkpoint inhibitors, such as anti-CTLA-4 and PD-1 monoclonal antibodies has enabled the modulation of T cell functions, consequently eliminating immunosuppression in the tumor microenvironment. Clinical trials were conducted using nivolumab and ipilimumab, which confirmed their clinical usefulness. The approval by FDA of nivolumab in treatment of recurrent and metastatic squamous cell carcinoma of the head and neck has increased the overall survival time of patients as well as disease free survival. Statistical data indicate an advantage of immunotherapy over other treatment methods at an advanced stage of cancer. This work aims to discuss basic issues related to immunotherapy, in particular immunotherapy in patients with squamous cell carcinoma of the head and neck.

11

Cardiovascular complications of selected antibodies used in oncological immunotherapy

75%

Kufel-Grabowska J.

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EN

Immunotherapy supports other therapeutic methods and is an important element in the fight against cancer. Its main tasks include stimulation and guidance of the immune system to fight cancer, inhibition of the mechanisms that block the immune system, and direct destruction of neoplastic cells. Different from chemotherapy or hormonal therapy, its mechanism of action is associated with a different profile of adverse events. HER2 receptor inhibitors may cause symptoms of heart failure, which usually recede, once the treatment has been discontinued. Bevacizumab, an anti-VEGF antibody, induces numerous cardiovascular complications, including arterial hypertension, arterial embolism, haemorrhage and haemoptysis as well as venous thromboembolism.

12

Immunologiczne aspekty choroby Alzheimera

75%

Wojtera M., Kłoszewska I., Sobów T., Liberski P. P.

Aktualności Neurologiczne

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2006

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vol. 6

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issue 2

108-115

EN

Alzheimer’s disease (AD) is an incurable neurodegenerative disease, which is accompanied by chronic inflammation. The immune system has an important role in the process of the disease. The deposition of amyloid β (Aβ) protein is a key pathological feature in Alzheimer’s disease. This article reviews immunotherapeutic strategies against AD. In murine models of AD, both active and passive immunization against Aβ induces a marked reduction in an amyloid brain burden and an improvement in cognitive functions. The findings from murine studies lead to clinical studies. One Phase II clinical trial of active immunization against Aβ was discontinued after 18 patients developed meningoencephalitis. After this lesson learned, new immunotherapeutic strategies, including both active and passive immunization, are investigated in clinical centers.

PL

Choroba Alzheimera (AD) jest nieuleczalną chorobą neurodegeneracyjną, której towarzyszy przewlekły proces zapalny. Układ immunologiczny może mieć istotny wpływ na przebieg procesu chorobowego. Głównym patologicznym wyznacznikiem choroby Alzheimera jest gromadzenie w obrębie mózgu złogów β-amyloidu. W obecnym artykule przedstawiono informacje na temat możliwości zastosowania immunoterapii w leczeniu choroby Alzheimera. Metody immunoterapeutyczne, mające usuwać amyloid β z chorych mózgów, dały bardzo pozytywne rezultaty w badaniach na zwierzętach. Zarówno metody aktywnej, jak i biernej immunizacji powodowały wyraźne zmniejszenie zawartości amyloidu w mózgach myszy transgenicznych oraz poprawę ich funkcji poznawczych. Bardzo dobre wyniki na modelach zwierzęcych pozwoliły przeprowadzić wstępne badania kliniczne. Ich wyniki są również obiecujące, choć obarczone ryzykiem zapalenia mózgu. Jedyne dotychczas badanie II Fazy z zastosowaniem szczepionki przeciwko Aβ zostało przerwane z powodu rozwoju u 18 pacjentów zapalenia opon mózgowych i mózgu. Obecnie ośrodkach badawczych pojawiają się nowe rodzaje technik immunoterapeutycznych.

13

The current state of knowledge on small cell and non-small cell lung cancer and the position of durvalumab immunotherapy in lung cancer treatment

75%

Poboży K., Domańska J., Domański P.

OncoReview

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2022

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vol. 12

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issue 4

75-82

EN

Lung cancer is the second most frequently diagnosed cancer and the leading cause of cancer-related deaths in the world. These statistics make lung cancer one of the most important targets for modern medicine. The identification of multiple risk factors, including tobacco smoking, has been fundamental in understanding the disease. Late-stage detection is a significant contributor to the high mortality rate of lung cancer. Nonetheless, the role of screening is still debatable. The selection of therapy is primarily based on distinguishing between small-cell and non-small cell lung cancer. Despite the major differences in treatment, in both types in specific situations the treatment involves durvalumab – a monoclonal antibody targeting the programmed cell death ligand 1 molecule, which is often present on tumor cells and protects them against the patient’s immune system. The efficacy of durvalumab has been demonstrated in two randomized, multicenter clinical trials. The aim of this study is to summarize the current state of knowledge about lung cancer and durvalumab. Despite the current 5-year survival rate of 19% in lung cancer, the development of immunotherapeutics such as durvalumab may be the key to improving the unfavorable prognosis of lung cancer in the future.

14

Salmonella and cancer: from pathogens to therapeutics

75%

Chorobik P., Czaplicki D., Ossysek K., Bereta J.

Acta Biochimica Polonica

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2013

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vol. 60

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issue 3

285-297

EN

Bacterial cancer therapy is a concept more than 100 years old - yet, all things considered, it is still in early development. While the use of many passive therapeutics is hindered by the complexity of tumor biology, bacteria offer unique features that can overcome these limitations. Microbial metabolism, motility and sensitivity can lead to site-specific treatment, highly focused on the tumor and safe to other tissues. Activation of tumor-specific immunity is another important mechanism of such therapies. Several bacterial strains have been evaluated as cancer therapeutics so far, Salmonella Typhimurium being one of the most promising. S. Typhimurium and its derivatives have been used both as direct tumoricidal agents and as cancer vaccine vectors. VNP20009, an attenuated mutant of S. Typhimurium, shows significant native toxicity against murine tumors and was studied in a first-in-man phase I clinical trial for toxicity and anticancer activity. While proved to be safe in cancer patients, insufficient tumor colonization of VNP20009 was identified as a major limitation for further clinical development. Antibody-fragment-based targeting of cancer cells is one of the few approaches proposed to overcome this drawback.

15

Advances in immunotherapy for osteosarcoma: a review of emerging treatment strategies

75%

Poboży K., Domański P., Domańska J., Konarski W., Poboży T.

OncoReview

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2023

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vol. 13

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issue 3

75-84

EN

Advances in immunotherapy for osteosarcoma have shown promising results, with the use of monoclonal antibodies and immune checkpoint inhibitors. These strategies are aimed at targeting specific molecules and pathways involved in tumour immune evasion and promoting anti-tumour immune responses. Other emerging immunotherapeutic approaches include autophagy and pyroptosis induction, chimeric antigen receptor T-cell therapy, gadolinium-bisphosphonate nanoparticles and dendritic cell-based vaccines. Continued research into these emerging treatment strategies is essential for developing effective therapies for patients with high-grade osteosarcoma.

16

Znaczenie PD-1 – receptora programowanej śmierci-1 – i jego ligandów w immunoterapii raka jajnika

75%

Markowska A., Sajdak S., Lubin J., Markowska J.

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issue 2

117-120

EN

The immune system plays an important role in both cancer development and destruction. Tumor cells have developed mechanisms to evade an effective immune response. One of these involves the use of immune checkpoint pathways, which modulate the intensity and duration of such responses. There are two immune checkpoint receptors that have been most thoroughly studied: CTLA-4 (cytotoxic T lymphocyte-associated antigen 4) and PD-1 (programmed cell death protein 1 pathway), involved in regulatory T cell responses. The anti-CTLA-4 antibody is used in the treatment of many malignancies, including non-small-cell lung cancer, prostate cancer and melanoma. PD-1 and its ligands, PD-L1 and PD-L2, represent an immune axis protecting cancer cells against regulatory T cells (cytotoxic CD8+ cells and CD4+ helper cells). Nivolumab, a monoclonal antibody, blocks PD-1 and, as a result, its binding to its ligands. Consequently, T cell antitumor activity is restored, which appears promising in clinical trials involving patients with malignancies in multiple locations, including non-small-cell lung cancer, melanoma and ovarian cancer, clear cell ovarian carcinoma in particular. Nivolumab therapy is not devoid of adverse effects, which affect about 40% of patients with ovarian cancer. These include e.g. arrhythmia, fever, anemia and decreased lymphocyte count. It is believed that combining a therapy that blocks the key immune checkpoints with other anticancer agents, including chemotherapy, radiation therapy or other targeted therapies, will improve treatment efficacy in malignancies, including ovarian cancer.

PL

Układ immunologiczny odgrywa istotną rolę zarówno w rozwoju raka, jak i jego destrukcji. Komórki nowotworu wykształciły mechanizmy pozwalające im uniknąć skutecznej reakcji immunologicznej. Jednym z nich jest wykorzystanie szlaków immunologicznych punktów kluczowych (immune checkpoint), które modulują nasilenie i czas trwania tej odpowiedzi. Najlepiej poznane są dwa receptory immunologicznych punktów kluczowych: antygen 4 CTLA (cytotoxic T lymphocyteassociated antigen 4) i białko programowanej śmierci komórki 1 – PD-1 (programmed cell death protein 1 pathway), uczestniczące w odpowiedzi regulatorowych limfocytów T. Przeciwciało przeciwko cząsteczce CTLA-4 stosowane jest w leczeniu wielu nowotworów złośliwych, w tym niedrobnokomórkowego raka płuca, raka prostaty i czerniaka. PD-1 i jego ligandy PD-L1 i PD-L2 stanowią oś immunologiczną, która chroni komórki nowotworowe przed działaniem limfocytów T regulatorowych (T cytotoksycznych CD8+ i pomocniczych CD4+). Przeciwciało monoklonalne niwolumab blokuje PD-1, a przez to połączenie z jego ligandami. W ten sposób odtwarzana jest aktywność przeciwguzowa limfocytów T, która okazuje się obiecująca w próbach klinicznych u chorych na nowotwory złośliwe w wielu lokalizacjach, w tym na niedrobnokomórkowego raka płuca, czerniaka oraz raka jajnika, zwłaszcza jasnokomórkowego. Stosowanie niwolumabu nie jest pozbawione działań niepożądanych, które występują u około 40% leczonych na raka jajnika kobiet. Należą do nich między innymi arytmia, gorączka, niedokrwistość oraz obniżenie liczby limfocytów. Uważa się, że łączenie terapii blokującej kluczowe punkty immunologiczne z innymi czynnikami przeciwrakowymi, w tym chemioterapią, radioterapią, inną terapią celowaną, pozwoli uzyskać większą skuteczność w leczeniu nowotworów złośliwych, w tym raka jajnika.

17

Alergenowo-swoista immunoterapia u dzieci

63%

Maślany A., Jung A.

Pediatria i Medycyna Rodzinna

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2011

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vol. 7

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issue 3

212-217

EN

Allergen-specific immunotherapy (ASI) allows for a treatment and influences on the course of, the allergic, IgE-dependent diseases. ASI induces allergen tolerance resulting in a reduction or disappearance of clinical symptoms of allergy. One hundred years ago, in 1910 exactly, Noon published his landmark study. Since then, the knowledge of its mechanisms, indications for ASI and routes of administration of allergen is systematically being broaden. Currently used forms of allergens allow to minimize serious side effects related to the ASI, which were observed in the initial trials of therapy. This paper presents current views on the pathomechanisms of immunotherapy, rules for an application of immunotherapy and possibility of using ASI in atopic diseases. The main reason for this form of a treatment is inability to eliminate the allergen from patient’s environment with a high probability of severe clinical symptoms after contact with the allergen. The best results are achieved in case of hypersensitivity to hymenoptera venom and treatment of allergic rhinitis, allergic conjunctivitis and asthma associated with allergy to grass pollen, trees, weeds and dust mites. Treatment of monoallergy gives better results compared to the sensitisation to multiple allergens. For some of the cases, due inability of pharmacotherapy or its ineffectiveness, one could consider usage of ASI for patients with allergy tied with other allergens. Currently this method is not approved for the treatment of food allergy. This paper quotes meta-analysis, carried out in recent years, evaluating the efficiency of the most popular current methods of immunotherapy – subcutaneous (SCIT) and sublingual (SLIT) – in the treatment of asthma and allergic rhinitis. The publications cited below clearly show that these methods are effective in reducing and eliminating allergy symptoms. This paper presents the latest promising route of administration allergen – percutaneous immunotherapy, particularly beneficial for younger patients. In the era of great advances in medicine, we can expect further improvements of ASI, elimination of serious side effects and widening group of patients eligible for this form of therapy.

PL

Alergenowo-swoista immunoterapia (ASI) umożliwia leczenie i wpływ na przebieg alergicznych schorzeń IgE-zależnych. W wyniku jej działania następuje indukcja tolerancji alergenu, a w rezultacie – zmniejszenie lub ustąpienie objawów klinicznych alergii. Od daty wydania (1910 r.) publikacji Noona, uważanej za przełomową w rozwoju immunoterapii, mija 101 lat. W tym czasie systematycznie poszerzano wiedzę na temat mechanizmów jej działania, wskazań do stosowania ASI oraz formy podawania alergenu. Obecnie stosowane rodzaje ASI pozwalają na zminimalizowanie poważnych objawów niepożądanych, które obserwowano w początkowych próbach terapii. W pracy przedstawiono współczesne poglądy na temat patomechanizmów immunoterapii, zasad jej podawania oraz możliwości stosowania ASI w przypadku schorzeń atopowych. Podstawowym wskazaniem do tej metody leczenia jest brak możliwości wyeliminowania alergenu ze środowiska pacjenta przy dużym prawdopodobieństwie wystąpienia ciężkich objawów klinicznych uczulenia po kontakcie z alergenem. Najlepsze rezultaty osiąga się w przypadku nadwrażliwości na jady owadów błonkoskrzydłych oraz leczenia alergicznego nieżytu nosa, alergicznego zapalenia spojówek, a także astmy związanej z alergią na pyłki traw, drzew, chwastów i roztoczy kurzu domowego. Leczenie monoalergii daje lepszą skuteczność w porównaniu z uczuleniem na wiele alergenów. W wybranych przypadkach przy braku możliwości stosowania farmakoterapii lub jej nieskuteczności można rozważyć użycie ASI u pacjentów z alergią związaną z innymi alergenami. Aktualnie nie jest to metoda zaakceptowana w leczeniu alergii pokarmowej. W pracy przytoczono metaanalizy przeprowadzone w ostatnich latach, oceniające skuteczność dwóch najpopularniejszych obecnie metod immunoterapii – SCIT (śródskórnej) oraz SLIT (podjęzykowej) – w leczeniu astmy oraz alergicznego nieżytu nosa. Z cytowanych poniżej publikacji wynika, że są to metody skuteczne, zmniejszające lub eliminujące objawy choroby u alergików. Przedstawiono również najnowsze, bardzo obiecujące drogi podania alergenu, w tym przezskórną immunoterapię, szczególnie korzystną u najmłodszych pacjentów. W dobie ogromnego postępu medycyny należy oczekiwać dalszego udoskonalania ASI, eliminacji poważnych objawów ubocznych oraz rozszerzenia grupy pacjentów objętych tą formą terapii.

18

Farmakoterapia dysfunkcji poznawczych w chorobie Alzheimera: obecne strategie i terapie eksperymentalne

63%

Sobów T.

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2013

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vol. 13

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issue 4

287-294

EN

Currently available methods of pharmacological treatment of cognitive dysfunction related to Alzheimer’s disease (AD) are based on augmentation of cholinergic neurotransmission (by inhibiting activity of cholinesterases) or modulation of glutamatergic transmission (by acting on NMDA receptor). Both classes of drug exhibit clinically significant (though modest) symptomatic improvement not only considering cognition but also behaviour and activities of daily living. Whether or not they modify natural course of the disease, is not clearly confirmed by result of rigorously planned clinical trials and is currently considered unlikely. With the development of genetic and molecular studies on the pathogenesis of AD novel treatment targets emerged recently, importantly these based on amyloid cascade hypothesis and τ protein phosphorylation. Unfortunately, the so far undertaken clinical trials yielded disappointing results, either proving not be effective or showing unfavourable side effects profile. The most commonly proposed explanations of these failures include starting trials too late during the disease process and/or insufficiently specific strategies of patients’ selection resulting in inclusion of subjects suffering from other than AD cognitive dysfunctions. Biomarkers of disease-specific process are currently leading answer to the experienced trials failures as they are starting to be routinely used in novel studies.

PL

Obecnie dostępne metody farmakologicznego leczenia zaburzeń funkcji poznawczych w chorobie Alzheimera (Alzheimer’s disease, AD) opierają się na potencjalizacji przekaźnictwa cholinergicznego (inhibitory cholinesteraz) oraz modulowaniu przekaźnictwa glutaminianergicznego (memantyna). Leki te wywierają zauważalny efekt objawowy w zakresie nie tylko funkcji poznawczych, lecz także zachowania i codziennej aktywności. Ich wpływ na naturalny przebieg choroby nie został jak dotąd jednoznacznie potwierdzony i ze względu na mechanizm działania jest uważany za mało prawdopodobny. Wraz z rozwojem badań genetycznych i molekularnych nad patogenezą AD do prób klinicznych wchodzą leki, które mają bezpośrednio oddziaływać na procesy odpowiedzialne za neurodegenerację i prowadzące do neurotoksycznego działania oligomerów i odkładania się w mózgu złogów białkowych. Niestety, przeprowadzone dotąd badania kliniczne zawiodły oczekiwania – nie potwierdziły skuteczności klinicznej i/lub wskazały na problemy z bezpieczeństwem leczenia. Najczęściej wymienianymi przyczynami tych niepowodzeń mają być podawanie leków w zbyt późnym stadium choroby i/lub niewystarczająco selektywne strategie doboru pacjentów, skutkujące włączaniem do badań chorych cierpiących na inne niż AD przyczyny zaburzeń poznawczych. Proponowaną odpowiedzią na niepowodzenia prób klinicznych ma być inkorporowanie biomarkerów procesu chorobowego do nowych badań.

19

Terapia rituksymabem w uogólnionej miastenii lekoopornej. Opis przypadku

63%

Bonek R., Maciejek Z., Radziszewski K.

Aktualności Neurologiczne

|

2009

|

vol. 9

|

issue 1

63-66

EN

Background: Rituximab is a human-mouse chimeric IgG1 monoclonal antibody directed against antigen CD-20, transmembrane phosphoprotein on B cells. This drug induce depletion of B cells and subsequent reduction in antibody production. Recently there were cases of severe AChR-antibody positive and MuSK-positive myasthenia gravis (MG) successfully treated with rituximab. Case report: Forty-three-year-old women with tygorefractory MG with predominantly generalised weakness in extremities, bulbar symptoms and dyspnea, who presented for the first time in 1992. Thymectomy was perform in 1997. During 15 years of therapy patient had one crise in 1997 and one in 1999. In 2007, she had five hospital admission. She did not respond adequately to acetylcholinesterase inhibitors, thymectomy, repeat plasma exchange and conventional immunosuppressive therapy such as azathioprine, cyclophosphamide and prednisone. For this reason rituximab (MabThera®, Roche) therapy was added. Rituximab was administered at a dose of 375 mg/m2 intravenously according to a protocol every 7 days for 4 weeks. She received also prednisone at a dose of 20 mg and pyridostigmine 180 mg per day all the time. Within 4 weeks therapy she showed maintained clinical improvement. Dyspnea and bulbar symptoms were disappearanced and walking distances was longer. We did not observe serious adverse events, only after first infusion transient oedema of mucosa nasal and oral cavity with concurrent pruritus and after second infusion transient myalgia, chills and subfebrile body temperature were found. Conclusions: In this case use of rituximab leading to significant clinical improvement in refractory myasthenia gravis. The therapy was well tolerated and any serious adverse events were registered.

PL

Wstęp: Rituksymab jest chimerycznym przeciwciałem monoklonalnym klasy IgG1, skierowanym przeciwko antygenowi CD20, przezbłonowej fosfoproteinie limfocytów B. Indukuje on deplecję limfocytów B, a w związku z tym spadek produkcji przeciwciał. Ostatnio opisywano przypadki zakończonego sukcesem leczenia rituksymabem ciężkiej miastenii (MG) seropozytywnej i miastenii z obecnością przeciwciał anty-MuSK. Opis przypadku: Czterdziestotrzyletnia kobieta z lekooporną miastenią z dominującym osłabieniem kończyn, objawami opuszkowymi i dusznością, z pierwszymi objawami choroby w 1992 roku. W 1997 roku wystąpił pierwszy przełom miasteniczny, w 1999 drugi. W roku 2007 z powodu zaostrzeń choroby pacjentka była pięciokrotnie hospitalizowana. W trakcie piętnastoletniej kuracji nie uzyskano zadowalającej odpowiedzi na inhibitory acetylocholinoesterazy, tymektomię, powtarzane zabiegi plazmaferezy i konwencjonalne leczenie immunosupresyjne, w którym zastosowano azatioprynę, cyklofosfamid i prednizon. Z tych względów włączono terapię rituksymabem (MabThera®, Roche). Rituksymab podawano we wlewie dożylnym zgodnie z następującym protokołem: 375 mg/m2 co 7 dni przez 4 tygodnie. Przez cały czas chora była leczona prednizonem w dawce 20 mg i pirydostygminą w dawce 180 mg na dobę. W trakcie terapii osiągnięto znaczącą poprawę stanu klinicznego, która utrzymuje się do chwili obecnej. Uzyskano ustąpienie duszności i objawów opuszkowych oraz wydłużenie przechodzonego dystansu. Nie stwierdzono poważnych działań niepożądanych; po pierwszym wlewie wystąpił przemijający obrzęk śluzówki jamy ustnej i nosowej z towarzyszącym świądem, a po drugim ból mięśni, dreszcze i stan podgorączkowy. Wnioski:W opisanym przypadku zastosowanie rituksymabu doprowadziło do znaczącej i długotrwałej poprawy klinicznej w przebiegu miastenii lekoopornej. Terapia była dobrze tolerowana i nie zaobserwowano żadnych poważnych działań niepożądanych.

20

Indukcja tolerancji w alergii na pokarmy

51%

Krogulska A.

Alergia Astma Immunologia - przegląd kliniczny

|

2020

|

vol. 25

|

issue 1

8-18

EN

Food allergy is a disease with a risk of anaphylactic reactions, including death, with an increasing incidence. New methods of treatment and prevention are constantly being studied. Such hopes are created by the induction of tolerance, which is a process that is disturbed in patients with food allergy. In the first part of the article, methods of tolerance induction in primary food allergy prevention are discussed, such as exposure to allergens, breastfeeding, the importance of dietary factors and microbiome. The second part discusses the importance of immunotherapy in the induction of tolerance in patients with already developed food allergy and compared it to standard treatment method, which is the elimination diet. The reader will find information about methods, indications, contraindications, pathomechanism, effectiveness, safety and a new methods of desensitization

PL

Alergia pokarmowa to choroba obarczona ryzykiem wystąpienia reakcji anafilaktycznych, łącznie ze zgonem, o narastającej częstości występowania. Stale poszukuje się nowych metod jej leczenia i prewencji. Takie nadzieje stwarza indukcja tolerancji, czyli procesu, który ulega zaburzeniu w jej przebiegu. W pierwszej części artykułu omówione są metody indukcji tolerancji w prewencji pierwotnej alergii pokarmowej, takie jak: ekspozycja na alergeny, karmienie piersią, znaczenie składników dietetycznych i mikrobiomu. W drugiej części omówiono znaczenie immunoterapii w indukcji tolerancji u pacjentów z już rozwiniętą alergią pokarmową i porównano ją do standardowych metod leczenia, jaką jest dieta eliminacyjna. Czytelnik znajdzie tu informacje na temat metod, wskazań, przeciwwskazań, patomechanizmu, skuteczności, bezpieczeństwa oraz nowych metod odczulania.

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