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Does the Immunocompetent Status of Cancer Patients Have an Impact on Therapeutic DC Vaccination Strategies?

Although different types of therapeutic vaccines against established cancerous lesions in various indications have been developed since the 1990s, their clinical benefit is still very limited. This observed lack of effectiveness in cancer eradication may be partially due to the often deficient immunocompetent status of cancer patients, which may facilitate tumor development by different mechanisms, including immune evasion. The most frequently used cellular vehicle in clinical trials are dendritic cells (DCs), thanks to their crucial role in initiating and directing immune responses. Viable va

Monoclonal Gammopathies of Clinical Significance: A Critical Appraisal.

Monoclonal gammopathies of clinical significance (MGCSs) represent a group of diseases featuring the association of a nonmalignant B cells or plasma cells clone, the production of an M-protein, and singularly, the existence of organ damage. They present a current framework that is difficult to approach from a practical clinical perspective. Several points should be addressed in order to move further toward a better understanding. Overall, these entities are only partially included in the international classifications of diseases. Its definition and classification remain ambiguous. Remarkably,

Targeting the gut microbiota to enhance the antitumor efficacy and attenuate the toxicity of CAR-T cell therapy: a new hope?

Chimeric antigen receptor (CAR) -T cell therapy has achieved tremendous efficacy in the treatment of hematologic malignancies and represents a promising treatment regimen for cancer. Despite the striking response in patients with hematologic malignancies, most patients with solid tumors treated with CAR-T cells have a low response rate and experience major adverse effects, which indicates the need for biomarkers that can predict and improve clinical outcomes with future CAR-T cell treatments. Recently, the role of the gut microbiota in cancer therapy has been established, and growing evidence

Pursuing a Curative Approach in Multiple Myeloma: A Review of New Therapeutic Strategies.

Multiple myeloma (MM) is still considered an incurable hematologic cancer and, in the last decades, the treatment goal has been to obtain a long-lasting disease control. However, the recent availability of new effective drugs has led to unprecedented high-quality responses and prolonged progression-free survival and overall survival. The improvement of response rates has prompted the development of new, very sensitive methods to measure residual disease, even when monoclonal components become undetectable in patients' serum and urine. Several scientific efforts have been made to develop reliab

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… Myeloma MRD by deep sequencing from circulating tumor DNA does not correlate with results obtained in the bone marrow Blood Adv. 2018 2 2811 2813 10.1182/bloodadvances.2018025197 30355580 PMC6234381 40. Avet-Loiseau H. San-Miguel J.F. Casneuf T. Iida S. Lonial S. Usmani S.Z. Spencer A. Moreau P. …

Anticancer Activities of Novel Nicotinamide Phosphoribosyltransferase Inhibitors in Hematological Malignancies.

Targeting cancer cells that are highly dependent on the nicotinamide adenine dinucleotide (NAD+) metabolite is a promising therapeutic strategy. Nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme catalyzing NAD+ production. Despite the high efficacy of several developed NAMPT inhibitors (i.e., FK866 (APO866)) in preclinical studies, their clinical activity was proven to be limited. Here, we report the synthesis of new NAMPT Inhibitors, JJ08, FEI191 and FEI199, which exhibit a broad anticancer activity in vitro. Results show that these compounds are potent NAMPT inhibito

The role of mesenchymal stem cells in attenuating inflammatory bowel disease through ubiquitination.

Inflammatory bowel disease (IBD), a condition of the digestive tract and one of the autoimmune diseases, is becoming a disease of significant global public health concern and substantial clinical burden. Various signaling pathways have been documented to modulate IBD, but the exact activation and regulatory mechanisms have not been fully clarified; thus, a need for constant exploration of the molecules and pathways that play key roles in the development of IBD. In recent years, several protein post-translational modification pathways, such as ubiquitination, phosphorylation, methylation, acety

Pediatric Drug Development: Reviewing Challenges and Opportunities by Tracking Innovative Therapies.

The paradigm of pediatric drug development has been evolving in a "carrot-and-stick"-based tactic to address population-specific issues. However, the off-label prescription of adult medicines to pediatric patients remains a feature of clinical practice, which may compromise the age-appropriate evaluation of treatments. Therefore, the United States and the European Pediatric Formulation Initiative have recommended applying nanotechnology-based delivery systems to tackle some of these challenges, particularly applying inorganic, polymeric, and lipid-based nanoparticles. Connected with these, adv

Immunological Targets in Generalized Myasthenia Gravis Treatment: Where Are We Going Now?

BackgroundGeneralized myasthenia gravis (gMG) is a heterogeneous autoimmune disorder marked by antibody-mediated disruption of neuromuscular transmission. Despite advancements in immunosuppressive therapies and biologics, a subset of patients remains refractory, necessitating more targeted and personalized treatment strategies.ObjectiveThis review aims to synthesize current knowledge of the immunopathological mechanisms across gMG subtypes and to explore emerging therapeutic targets tailored to these diverse disease phenotypes.MethodsA narrative review was conducted, integrating recent finding

Молекулярные модели, связанные с ущербом от митохондриала: нейроиммуномодуляторы в патофизиологии центральной нервной системы.

Нейроинфламмация способствует широкому спектру нейродегенеративных заболеваний, включая болезнь Альцгеймера, болезнь Паркинсона, болезнь Хантингтона и множественный склероз. Его движут неевропейские глиальные клетки, главным образом микроглии и астроциты. Микроглии являются постоянными иммунными клетками центральной нервной системы, в то время как астроциты являются основными элементами поддержки нейронных функций, но могут также участвовать в нейроиммунной реакции. Оба этих типа глиальных клеток могут стать реактивными при обнаружении определенных внутриклеточных молекул, которые появляются в

Cancer Therapy and Exercise Intolerance: The Heart Is But a Part: JACC: CardioOncology State-of-the-Art Review.

The landscape of cancer therapeutics is continually evolving, with successes in improved survivorship and reduced disease progression for many patients with cancer. Improved cancer outcomes expose competing comorbidities, some of which may be exacerbated by cancer therapies. The leading cause of disability and death for many early-stage cancers is cardiovascular disease (CVD), which is often attributed to direct or indirect cardiac injury from cancer therapy. In this review, the authors propose that toxicities related to conventional and novel cancer therapeutics should be considered beyond th

Advances and prospects in cell therapy for cancer: explorations from T cells to stem cells.

The increasing global burden of cancer necessitates innovative therapeutic strategies. Cell therapy represents a major breakthrough in oncology, evolving rapidly from the successful application of chimeric antigen receptor T (CAR-T) cells in hematologic malignancies to a multiplatform landscape characterized by the concurrent development of diverse strategies. Current research focuses on T cell receptor-engineered T (TCR-T) cells, tumor-infiltrating lymphocytes (TILs), gamma delta (γδ) T cells, CAR-natural killer (CAR-NK) cells, CAR-macrophages (CAR-Ms), and various strategies based on dendrit

Intestinal Microbes and Hematological Malignancies.

Hematological malignancies are diverse, with high malignancy characteristics, poor prognoses, and high mortality rates. The development of hematological malignancies is driven by genetic factors, tumor microenvironment factors, or metabolic factors; however, even when considering all of these factors, one still cannot fully estimate the risk of hematological malignancies. Several recent studies have demonstrated an intimate connection between intestinal microbes and the progression of hematological malignancies, and gut microbes play a primary role in the initiation and progression of hematolo

Терапевтическое применение иммунобиологии в аутоиммунных и воспаленных заболеваниях.

Иммунобиологика или биологическая экспертиза революционизировали терапевтическую парадигму аутоиммунных и подстрекательских заболеваний путем выборочного целеопределения и модуляции дисрегулированных иммунных путей. По сравнению с обычными широкоспектральными иммунопрепрессантами биологика обеспечивает более конкретный и основанный на механизмах рациональный подход, зачастую связанный с повышением эффективности и сокращением неблагоприятных явлений. В этом обзоре содержится всеобъемлющий обзор репертуара терапевтической биологики, механизмов их действий, важнейших клинических испытаний и клини

Декодирование GPCR, сигнализирующее перепрограммирование рака: молекулярные механизмы и терапевтические последствия.

G белковые рецепторы (GPCR) представляют собой крупнейшую мембранную группу рецепторов в геноме человека и служат ключевыми регуляторами клеточного сигнала, гомеостаза и фармакологической реакции. Помимо их классической роли в посредничестве внеклеточной стимуляции по зависящим от G-протеина и независимым путям, которые играют ключевую роль при помощи GPCR сигнальных путей, включая CAMP-PKA/EPAC, IP3/PLC, PI3K/Akt/mTOR и ERK/MAPK cascades, в вождении онкогенного распространения, апоптоза и метастаза. Кроме того, ГПХР замешаны в опухоли с помощью различных молекулярных механизмов, в рамках кото

Hypoxia within the glioblastoma tumor microenvironment: a master saboteur of novel treatments.

Glioblastoma (GBM) tumors are the most aggressive primary brain tumors in adults that, despite maximum treatment, carry a dismal prognosis. GBM tumors exhibit tissue hypoxia, which promotes tumor aggressiveness and maintenance of glioma stem cells and creates an overall immunosuppressive landscape. This article reviews how hypoxic conditions overlap with inflammatory responses, favoring the proliferation of immunosuppressive cells and inhibiting cytotoxic T cell development. Immunotherapies, including vaccines, immune checkpoint inhibitors, and CAR-T cell therapy, represent promising avenues f

Ущерб от белой материи при нарушении центральной нервной системы.

По мере ускорения процесса старения и улучшения условий жизни болезни центральной нервной системы (СНС) стали одной из основных проблем здравоохранения. Болезни CNS вызывают не только повреждения серых веществ, которые в первую очередь характеризуются потерей нейронов, но и повреждения белых веществ. Однако в большинстве предыдущих исследований основное внимание уделялось травматизму серого вещества (ГМИ), при этом было проведено меньше исследований травматизма белого вещества (ВМИ). В этой статье мы кратко опишем структуру и функцию белого вещества, подытожим патологические изменения ВМИ и со

Double Repositioning: Veterinary Antiparasitic to Human Anticancer.

Drug repositioning, the approach of discovering different uses for existing drugs, has gained enormous popularity in recent years in the anticancer drug discovery field due to the increasing demand for anticancer drugs. Additionally, the repurposing of veterinary antiparasitic drugs for the treatment of cancer is gaining traction, as supported by existing literature. A prominent example is the proposal to implement the use of veterinary antiparasitics such as benzimidazole carbamates and halogenated salicylanilides as novel anticancer drugs. These agents have revealed pronounced anti-tumor act

Expression and clinical significance of programmed death ligand-1 evaluated by 22C3 antibody in pleural effusion metastatic non-small-cell lung cancer.

ObjectiveProgrammed death ligand-1 (PD-L1) is involved in tumor immune escape and is an important target molecule for the immunotherapy of non-small-cell lung cancer (NSCLC). The expression of PD-L1 affects NSCLC invasion, metastasis, and patient survival. This study aims to explore the levels of PD-L1, as identified by the 22C3 antibody, in the malignant pleural effusion of patients suffering from advanced NSCLC, and to determine its clinical implications.Material and methodsA two-step immunohistochemical EnVision assay was used to evaluate the expression of PD-L1 by the 22C3 antibody in 149

61st Annual Conference of Indian Society of Gastroenterology, Virtual Diamond Jubilee ISGCON 2020, 19-20th December 2020.

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Объединение АИ, вакцин РНК и ЦАР-Т ячеек для индивидуального лечения.

Онкология претерпевает глубокие преобразования, вызванные конвергенцией искусственного интеллекта (AI), вакцин на основе РНК и химерика антигенного рецептора Т-клеток (CAR-T). В индивидуальном порядке эти технологии позволяют диагностировать рак, лечить и стратифицировать пациента. Подходы, основанные на принципе АИ, способствуют обнаружению наркотиков, оптимизации клинических опытных разработок и создают возможности для индивидуализированного терапевтического принятия решений. Вакцины RNA обеспечивают гибкую платформу для кодирования неонантигенов опухоли, в то время как CAR-T-терапия дает во

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… These include computational neoantigen prediction, RNA vaccine design, CAR‐T antigen target selection, and posttreatment immune monitoring using tools such as sequencing, flow cytometry, or circulating tumor DNA analysis. However, other elements remain experimental. …