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Blocking the MIF-CD74 axis augments radiotherapy efficacy for brain metastasis in NSCLC via synergistically promoting microglia M1 polarization.

BackgroundBrain metastasis is one of the main causes of recurrence and death in non-small cell lung cancer (NSCLC). Although radiotherapy is the main local therapy for brain metastasis, it is inevitable that some cancer cells become resistant to radiation. Microglia, as macrophages colonized in the brain, play an important role in the tumor microenvironment. Radiotherapy could activate microglia to polarize into both the M1 and M2 phenotypes. Therefore, searching for crosstalk molecules within the microenvironment that can specifically regulate the polarization of microglia is a potential stra

Increased Indoleamine 2, 3-Dioxygenase expression modulates Th1/Th17/Th22 and Treg pathway in humans with Helicobacter Pylori-Infected gastric mucosa.

Introduction and purposeIndoleamine 2, 3- dioxygenase (IDO) plays an importantrole in immunosuppressive pathway, as inhibits responsesof T cells and promotes immune tolerance. Host responsetoHelicobacter pylori (H. pylori) is involved in the infection persistenceand it is also associatedwith different clinical outcomes. The aim of this study was to investigate the role of IDO in H. pylori-infected patients with gastritis diseases and peptic ulcer diseases (PUD) through the assessment of the relationship among IDO protein expression and the numbers of T helper (Th)-1, Th17, Th22, and T regulato

The progress of novel strategies on immune-based therapy in relapsed or refractory diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) can be cured with standard front-line immunochemotherapy, whereas nearly 30-40% of patients experience refractory or relapse. For several decades, the standard treatment strategy for fit relapsed/refractory (R/R) DLBCL patients has been high-dose chemotherapy followed by autologous hematopoietic stem cell transplant (auto-SCT). However, the patients who failed in salvage treatment or those ineligible for subsequent auto-SCT have dismal outcomes. Several immune-based therapies have been developed, including monoclonal antibodies, antibody-drug conjugates, b

CAR-T in relapsed refractory high-grade glioma and glioblastoma - who, what, when and how?

Recurrent high-grade gliomas have a dismal prognosis. This review article aimed to explore and help answer the questions about which group of patients would benefit from chimeric antigen receptor therapy (CAR-T) cell therapy in this setting, the timing of intervention and the therapeutic efficacy. CAR-T cell therapy involves the extraction of T-cells from patients, genetic modification of these cells to express chimeric antigen receptors on their cell surface, which are selectively targeted towards tumour-expressed antigens and a procedure of immune-depletion followed by re-introducing these e

Management of refractory autoimmune hemolytic anemia after allogeneic hematopoietic stem cell transplantation: current perspectives.

Autoimmune hemolytic anemia (AIHA) is increasingly observed after allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a reported incidence between 4% and 6%. The disease is generally severe and refractory to standard therapy, with high mortality, and there are neither defined therapies, nor prospective clinical trials addressing the best treatment. Most of the knowledge on the therapy of AIHAs derives from primary forms, which are highly heterogeneous as well, further complicating the management of post-allo-HSCT forms. The review addresses the risk factors associated with pos

Monoclonal Antibodies Approved for Cancer Therapy

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Enhancing CAR T cells function: role of immunomodulators in cancer immunotherapy.

CAR T-cell therapy is a promising immunotherapy, providing successful results for cancer patients who are unresponsive to standard and traditional therapeutic approaches. However, there are limiting factors which create a hurdle in the therapy performing its role optimally. CAR T cells get exhausted, produce active antitumor responses, and might even produce toxic reactions. Specifically, in the case of solid tumors, chimeric antigen receptor T (CAR-T) cells fail to produce the desired outcomes. Then, the need to use supplementary agents such as immune system modifying immunomodulatory agents

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… The optimal antigen response of chimeric antigen receptors harboring the CD3zeta transmembrane domain is dependent upon incorporation of the receptor into the endogenous TCR/CD3 complex. J Immunol. 2010;184(12):6938–49. 10.4049/JIMMUNOL.0901766. 29. Haiyuan Y, Pan J, Guo Z, Yang C, Mao L. …

Targeting B Cell Maturation Antigen in Patients with Multiple Myeloma: Current Perspectives.

Relapsed/refractory multiple myeloma remains a challenging disease necessitating the development of more effective treatment options. In the past decade, myeloma therapies have made significant advancements with the introduction of new treatment modalities. One of the new major targets for these novel therapeutics has been B-cell maturation antigen (BCMA), which is expressed on mature B-lymphocytes and plasma cells. There are three main categories of BCMA-targeted therapies currently available, including bispecific antibodies (BsAbs), antibody drug conjugates (ADCs), and chimeric antigen recep

Редкое дерматологическое проявление фолликулярных смешений у пациента с множественной миеломой и конечной стадией почечной болезни при гемодиализе: отчет по делу.

Множественная миелома (ММ) — гематологическая порча, характеризующаяся клональным расширением злокачественных плазменных клеток в костном мозге, что приводит к различным системным осложнениям. Хотя резкие проявления MM редки, фолликулы представляют собой весьма специфический, но редкий дерматологический вывод, связанный с MM. В настоящем исследовании представлен пример 59-year-old Человек с MM, который демонстрировал фолликулярный акантоз и гиперкератоз в качестве скромных индикаторов злодеяний. Пациент с историей сцены 5 В ходе клинической оценки и лабораторных исследований был диагностирован

Tocilizumab Dosing for Management of T Cell-Engaging Bispecific Antibody-Related CRS in Patients With R/R B-Cell NHL.

The recent surge in T-cell-engaging and chimeric antigen receptor (CAR) T-cell therapies is changing the landscape of cancer therapy. Cytokine release syndrome (CRS) is a systemic inflammatory response syndrome that is a well-known complication of these therapies, of which interleukin-6 (IL-6) is a key mediator. Tocilizumab, an IL-6 receptor (IL-6R) antagonist, is approved for the management of CAR T-cell therapy-induced CRS in adults and in pediatric patients aged ≥ 2 years old. However, the approved dosing schedule was not based on IL-6R occupancy and may not be the most suitable schedule fo

2018 Ежегодное совещание СНГ: Североамериканская конференция по вопросам неадекватности и регулирования.

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Concurrent chronic lymphocytic leukemia and primary hyperparathyroidism in a mule.

A 26-year-old mule gelding was evaluated for chronic weight loss and decreased appetite. The mule had been losing weight and intermittently hypophagic for approximately 7 months. Laboratory analysis of whole blood and plasma identified severe total hypercalcemia, marked hypophosphatemia, markedly increased parathyroid hormone concentration, and marked lymphocytosis. A sestimibi scan intended to identify parathyroid gland tissue was nondiagnostic. Results of flow cytometry and PCR for antigen receptor rearrangement (PARR) were consistent with a B cell lymphoproliferative disorder, likely chroni

Амбулаторное расширение дозирования би специфических антител в реанимированных или рефрактных множественных миеломах: онкологическая система ухода за больными для мониторинга и оказания поддержки.

Биконкретные антитела расширили возможности лечения повторной или рефрактной множественной миеломы, однако начало лечения по-прежнему сопряжено с трудностями в оперативном плане, поскольку повышение уровня дозирования конкретных продуктов концентрирует наибольший риск ранней иммунной токсичности. В этом структурном обзоре описательной части обобщаются имеющаяся информация о предписаниях, отчеты о клинической безопасности, экспертные рекомендации, имплементационная литература и соответствующие данные об оказании помощи медсестрам в целях расширения масштабов амбулаторного дозирования. Мы пересм

The War Is on: The Immune System against Glioblastoma-How Can NK Cells Drive This Battle?

Natural killer (NK) cells are innate lymphocytes that play an important role in immunosurveillance, acting alongside other immune cells in the response against various types of malignant tumors and the prevention of metastasis. Since their discovery in the 1970s, they have been thoroughly studied for their capacity to kill neoplastic cells without the need for previous sensitization, executing rapid and robust cytotoxic activity, but also helper functions. In agreement with this, NK cells are being exploited in many ways to treat cancer. The broad arsenal of NK-based therapies includes adoptiv

Blood biomarker dynamics in people with relapsing multiple sclerosis treated with cladribine tablets: results of the 2-year MAGNIFY-MS study.

BACKGROUND AND OBJECTIVES: Cladribine tablets (CladT) represent an effective immune reconstitution therapy, administered in short treatment courses over two consecutive years. To better understand the amplitude of immune changes, we performed a comprehensive analysis during the 2-year study period for the entire MAGNIFY-MS population (N=270). In addition to lymphocyte kinetics, we studied intracellular cytokines serum proteins, and their associations with clinical outcomes. To put these changes into perspective, we analyzed transcriptional changes in T and B cells and associated biological pat

Bispecific antibodies in the treatment of multiple myeloma.

The treatment paradigm in myeloma is constantly changing. Upfront use of monoclonal antibodies like daratumumab along with proteasome inhibitors (PI)s, and immune modulators (IMiD)s have significantly improved survival and outcomes, but also cause unique challenges at the time of relapse. Engaging immune T cells for tumour cell kill with chimeric antigenic T-cell (CAR T-cell) therapy and bispecific antibodies have become important therapeutic options in relapsed multiple myeloma. Bispecific antibodies are dual antigen targeting constructs that engage the T cells to plasma cells through various

Кардиотоксичность, вызванная множественными миэломатерапиями: механистическая конвергенция между протеиновыми ингибиторами, CAR-T и биконкретными антителами.

Сердечно-сосудистая токсичность стала важным препятствием на пути реализации полного клинического потенциала современной терапии для множественных миэломы (ММ), включая протеазонные ингибиторы (ИП), химерика антигенного рецептора Т-клеток (CAR-T) и CD3-engaging Биотипные антитела. Здесь мы обсуждаем эпидемиологию, лежащую в основе механистических путей, и новые стратегии предотвращения кардиотоксичности, вызванной терапией, в MM. На основе данных, полученных в ходе исследований по изучению мультиомики, доклинических моделей и данных наблюдений в реальном мире, мы синтезируем вклад митохондриал

Протеомический анализ показывает дисрегламентацию периферийных нейтрофилов крови у пациентов с множественным склерозом.

Множественный склероз (MS) представляет собой сложное автовоспалительное заболевание мозга и спинного мозга, которое приводит к аксоновому демилеляции и симптомам, включая усталость, боль и трудности с зрением и мобильностью. Вовлеченность иммунной системы в патологию MS хорошо известна, в частности адаптивная реакция T-клеток, и особое внимание уделяется производящему IL-17 поднабору клеток TH17 и их роли в вождении болезней. Однако важность врожденных иммунных клеток не была столь хорошо охарактеризована. Здесь мы сосредоточили внимание на нейтрофилах, которые являются врожденными иммунными

B7-H3 (CD276) as Target for T Cell-Based Bispecific Antibody Therapy of Penile Cancer.

IntroductionMetastatic or locally advanced penile cancer (PeCa) has limited systemic treatment options and a 5-year survival rate of ~10% in metastatic disease. Using the in vitro and ex vivo models we preclinically assessed CC-3, a B7-H3xCD3 bispecific antibody (bsAb) currently in a Phase I basket trial (NCT05999396).MethodsPrimary PeCa cells were isolated from surgical specimens and characterized for surface antigen expression by flow cytometry (n = 4). B7-H3 expression was additionally evaluated in primary penile cancer tissues by immunohistochemistry (n = 10). The functional activity of th

Constructing the cure: engineering the next wave of antibody and cellular immune therapies.

Immuno-oncology has revolutionized cancer treatment by mobilizing the immune system to eliminate tumors. Although immune checkpoint inhibitors and T cell therapies have mediated durable responses in hematologic malignancies and select solid tumors, most patients still relapse or fail to respond. To overcome these limitations, novel, next-generation immune constructs, including bispecific-cell therapy combinations, armored cells, tethered cytokines, immune-stimulatory antibody conjugates, and in vivo gene editing, are being developed to enhance specificity, persistence, and immune activation. T