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Antibody-Drug Conjugates in Contemporary Oncology: A Clinical Perspective on Dose Optimization, Sequencing, and Combination Strategies.

Antibody-drug conjugates (ADCs) have matured from a technically challenging concept into an established therapeutic platform across hematologic and solid malignancies. By linking a monoclonal antibody to a potent cytotoxic payload, ADCs seek to increase tumor-directed drug delivery while limiting systemic exposure; however, clinical performance depends on much more than target expression. Target accessibility, antigen density and heterogeneity, internalization, intracellular trafficking, linker stability, payload properties, drug-to-antibody ratio, bystander effect, tumor penetration, and host

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

Epstein-Barr Virus Promotes Tumorigenicity and Worsens Hodgkin Lymphoma Prognosis by Activating JAK/STAT and NF-κB Signaling Pathways.

BACKGROUND: Epstein-Barr virus (EBV) is detected in 40% of patients with Hodgkin lymphoma (HL). During latency, EBV induces epigenetic alterations to the host genome and decreases the expression of pro-apoptotic proteins. The present study aimed to evaluate the expression levels of mRNA molecules and the end product of proteins for the JAK/STAT and NF-κB pathways, and their association with clinicopathological and prognostic parameters in patients with EBV-positive and -negative classical Hodgkin lymphoma (CHL). METHODS: A prospective cohort study was conducted from 2017 to 2022 at the Facult

Миэлоидно-подавительские клетки в карциноме ларингеальных клеток: недостаточно изученная иммунодепрессивная ось и стратегическая цель преодоления ингибиторного сопротивления на контрольно-пропускных пунктах.

Углубленные клеточные карциномы (LSCC) указывают на неизменно низкий коэффициент объективной реакции на ингибиторы на контрольно-пропускных пунктах (ИКИ) в отношении запрограммированных death-1 (В тыс.PD-1Путь. Его иммуновосприимчивая опухоль (TME), обогащенная макрофагами, связанными с опухолью, иммунодепрессивными опухолью, связанными с нейтрофилами (TANs), и регуляционными Т клетками, является основным фактором отказа ICI. Пока что one Миелоидное население, имеющее центральное значение для сопротивления ИКИ во многих случаях, не получает особого внимания в связи с этим заболеванием. Миелиои

NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma.

Despite recent therapeutic advances, multiple myeloma (MM) remains largely incurable. Here we report results of a phase I/II trial to evaluate the safety and activity of autologous T cells engineered to express an affinity-enhanced T cell receptor (TCR) recognizing a naturally processed peptide shared by the cancer-testis antigens NY-ESO-1 and LAGE-1. Twenty patients with antigen-positive MM received an average 2.4 × 10(9) engineered T cells 2 d after autologous stem cell transplant. Infusions were well tolerated without clinically apparent cytokine-release syndrome, despite high IL-6 levels.

Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia.

The limited sensitivity of the historical treatment response criteria for acute myeloid leukemia (AML) has resulted in a different paradigm for treatment compared with most other cancers presenting with widely disseminated disease. Initial cytotoxic induction chemotherapy is often able to reduce tumor burden to a level sufficient to meet the current criteria for "complete" remission. Nevertheless, most AML patients ultimately die from their disease, most commonly as clinically evident relapsed AML. Despite a variety of available salvage therapy options, prognosis in patients with relapsed or r

Nanotechnology-Driven Cancer Therapies for Precision Oncology: Advances and Clinical Outlook.

Cancer continues to pose a global health challenge, with conventional therapies often limited by non-specific toxicity, drug resistance, and an inadequate therapeutic index. Nanotechnology offers transformative opportunities by enabling targeted drug delivery, improved pharmacokinetics, and integrated diagnostic-therapeutic platforms (termed nanotheranostics). This review highlights key nanocarrier systems including liposomes, polymeric nanoparticles, dendrimers, inorganic nanostructures, carbon-based materials, extracellular vesicles, and hybrid platforms with a focus on human studies and cli

Melanoma and immunotherapy bridge 2015 : Naples, Italy. 1-5 December 2015.

MELANOMA BRIDGE 2015 KEYNOTE SPEAKER PRESENTATIONS Molecular and immuno-advances K1 Immunologic and metabolic consequences of PI3K/AKT/mTOR activation in melanoma Vashisht G. Y. Nanda, Weiyi Peng, Patrick Hwu, Michael A. Davies K2 Non-mutational adaptive changes in melanoma cells exposed to BRAF and MEK inhibitors help the establishment of drug resistance Gennaro Ciliberto, Luigi Fattore, Debora Malpicci, Luigi Aurisicchio, Paolo Antonio Ascierto, Carlo M. Croce, Rita Mancini K3 Tumor-intrinsic beta-catenin signaling mediates tumor-immune avoidance Stefani Spranger, Thomas F. Gajewski K4 Intra

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

Ремонтные механизмы центральной нервной системы: от вырастания аксона до воспроизводства.

Центральная нервная система (КНС), состоящая из мозга, спинного мозга и зрительного нерва, имеет ограниченную регенеративную способность, что создает значительные трудности в лечении неврологических расстройств. Последние достижения в области нейрофизики и нейротерапевтии ввели перспективные стратегии стимулирования восстановления CNS, особенно в контексте нейродегенеративных заболеваний, таких, как множественный склероз. В настоящем обзоре рассматривается сложная взаимосвязь между воспалением, обезвоживанием и возможностями воспоминания. Глиальные клетки, включая прекурсоры олигодендроцитов,

P2X7 Рецептор рентгеновских заболеваний: общие молекулярные механизмы и терапевтические последствия.

Редкие заболевания (РЛ) в индивидуальном порядке редко встречаются, но в совокупности они затрагивают большое число людей во всем мире, и подавляющее большинство из них по-прежнему не имеют эффективных методов лечения, позволяющих вести борьбу с заболеваниями. Благодаря достижениям в области геномики и платформ для обмена данными исследования все чаще переходят от одного заболевания к поиску конвергентных молекулярных путей, которые можно было бы использовать в различных клинически отличных друг от друга структурах. В этом контексте purinergic P2X7 рецептор (P2X7R) превратился в предполагаемую

Role of IL-5 in eosinophil-associated diseases and prospects for multi-target therapy.

Eosinophil-associated diseases are a group of inflammatory disorders characterized by abnormal eosinophil infiltration, which significantly impacts patients' quality of life. Interleukin-5 (IL-5), a critical cytokine that regulates eosinophil development, activation, chemotaxis, and survival, plays a central role in the pathogenesis of these diseases. This review systematically examines the molecular structure and signaling pathways of IL-5, its mechanisms of action in asthma and chronic obstructive pulmonary disease (COPD), and the development and clinical applications of monoclonal antibodie

Targeting the NLRP3 inflammasome in kidney disease: molecular mechanisms, pathogenic roles, and emerging small-molecule therapeutics.

Inflammatory responses represent a core pathological process driving the progression of both acute and chronic kidney diseases. As a key effector of the innate immune system, the NLRP3 inflammasome is widely activated in renal resident cellsand infiltrating immune cells, positioning it as a critical nexus linking metabolic dysregulation, cellular stress, and tissue injury. Accumulating preclinical and clinical evidence in recent years demonstrates that aberrant activation of the NLRP3 inflammasome directly promotes glomerular damage, tubulointerstitial inflammation, fibrosis, and vascular dysf

Critical considerations for targeting colorectal liver metastases with nanotechnology.

Colorectal cancer remains a significant cause of morbidity and mortality worldwide. Half of all patients develop liver metastases, presenting unique challenges for their treatment. The shortcomings of conventional chemotherapy has encouraged the use of nanomedicines; the application of nanotechnology in the diagnosis and treatment of disease. In spite of technological improvements in nanotechnology, the complexity of biological systems hinders the prospect of nanomedicines being applied in cancer therapy at the present time. This review highlights current biological barriers and discusses aspe

Novel immunotherapeutic strategies of gastric cancer treatment.

Gastric cancer (GC) is the fourth most common cancer and the second most frequent cause of cancer-related deaths, accounting for 10.4% of cancer deaths worldwide. Despite the improvements, estimated cure rates for patients with advanced stages remain poor, and in the metastatic setting, chemotherapy is the mainstay of palliative therapy and results in objective response rates (ORRs) of only 20-40% and median overall survivals (OS) of 8-10 months. Therefore, many investigators believe that the potential for making significant progress lies in understanding and exploiting the molecular biology o

Overcoming resistance to immune checkpoint inhibitor therapy in acute myeloid leukemia.

Acute myeloid leukemia (AML) is characterized by molecular, immunological, and clinical heterogeneity and this has been reflected with changing paradigms in the treatment landscape of AML in recent years. Despite high remission rates with conventional chemotherapy regimens, most patients eventually relapse and have disappointing outcomes in the relapsed setting, with estimated 5-year overall survival rates ranging from 10-15%. Immune checkpoint inhibitors (ICIs) restrain T-cell suppressive signals delivered through cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) or programmed cell death p

Совпадение в полном тексте источника
… BioMed Pharmacother . ( 2021 ) 137 : 111299 . doi: 10.1016/j.biopha.2021.111299 , PMID: 33508619 16 Fu C Liang X Cui W Ober-Blobaum JL Vazzana J Shrikant PA . beta-Catenin in dendritic cells exerts opposite functions in cross-priming and maintenance of CD8+ T cells through regulation of IL-10 . … GSK-3beta in dendritic cells exerts opposite functions in regulating cross-priming and memory CD8 T cell responses independent of beta-catenin . Vaccines (Basel) . ( 2024 ) 12 ., PMID: 39340067 10.3390/vaccines12091037 PMC11436163 18 Chang CH Qiu J O'Sullivan D Buck MD Noguchi T Curtis JD . …

Mucosal-Associated Invariant T Cells Display Diminished Effector Capacity in Oesophageal Adenocarcinoma.

Oesophageal adenocarcinoma (OAC) is an aggressive malignancy with poor prognosis, and incidence is increasing rapidly in the Western world. Mucosal-associated invariant T (MAIT) cells recognize bacterial metabolites and kill infected cells, yet their role in OAC is unknown. We aimed to elucidate the role of MAIT cells during cancer development by characterizing the frequency, phenotype, and function of MAIT cells in human blood and tissues, from OAC and its pre-malignant inflammatory condition Barrett's oesophagus (BO). Blood and tissues were phenotyped by flow cytometry and conditioned media

Unraveling the mechanisms of bone diseases: targeting dendritic cells in osteoimmunology for internal homeostasis balance.

Bone repair and regeneration is a complex spatiotemporal process recruiting a variety of cell types, which need to precisely mediated for effective healing post-damage. The concept of osteoimmunology emphasizes the extensive and intricate crosstalk between the bone and the immune system. Despite the significant advancements in understanding osteoimmunology, the precise role of dendritic cells (DCs) in this field remains under investigation. As key antigen-presenting cells, DCs are critical in orchestrating adaptive immune responses and maintaining tissue homeostasis. Recent researches have fur

Разногласия по полу в прогрессивном множестве склерозных генов мозга в олигодендроцитах и OPC.

Множественный склероз — это неврологическое аутоиммунное заболевание с сбалансированным по половому признаку коэффициентом заболеваемости; в США это заболевание с большей вероятностью воздействует на женщин в соотношении 3:1. Кроме того, во время диагностирования у мужчин больше шансов пройти курс лечения более тяжелыми заболеваниями. Сохраняются вопросы, касающиеся как причин, так и последствий такого неравенства. Мы пытаемся исследовать различия в экспрессии генов на клеточном уровне, рассматривая при этом секс, чтобы обнаружить тонкое гендерное неравенство. Эти расследования могли бы открыт

33rd Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2018) : Washington, D.C., USA. 7-11 November 2018.

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