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Bispecific and multispecific immune engagers for redirecting innate and adaptive immunity against hematologic cancers.

Bispecific antibodies (BsAbs) and multispecific antibodies (MsAbs) represent a transformative class of immunotherapeutics in oncology. These engineered molecules possess the unique ability to simultaneously target two or more distinct antigens, thereby facilitating precise immune cell engagement and disrupting multiple signaling pathways. This comprehensive review focuses on their pivotal role in redirecting both innate (natural killer cells, phagocytes) and adaptive (T cells) immunity, with a particular emphasis on their application against hematologic cancers. Significant clinical successes,

The Pharmacology of T Cell Therapies.

Adoptive cellular therapy using T cells with tumor specificity derived from either natural T cell receptors (TCRs) or an artificial chimeric antigen receptor (CAR) has reached late phase clinical testing, with two CAR T cell therapies achieving regulatory approval within the United States in 2017. The effective use of these therapies depends upon an understanding of their pharmacology, which is quite divergent from traditional small molecule or biologic drugs. We review the different types of T cell therapy under clinical development, the factors affecting cellular kinetics following infusion,

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… Genetic modification can be accomplished by use of retroviral vectors, 9 , 10 lentiviral vectors, 11 transposons, 12 or, most recently, homologous recombination following gene editing. 13 , 14 Defining the “Drug” in T Cell Therapies Drugs used in the clinical setting require production that adheres …

Unravelling T cell exhaustion through co-inhibitory receptors and its transformative role in cancer immunotherapy.

Persistent stimulation from cancer antigens leads to T lymphocytes (T cells) exhaustion, with up-regulated expression of co-inhibitory receptors, including programmed death-1 (PD-1), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3), T cell immunoglobulin and mucin domain 3 (TIM-3) and T cell immunoreceptor with Ig and ITIM domains (TIGIT). These receptors collectively impair T cell function via distinct molecular pathways, contributing to immune evasion and cancer progression. This review highlights the therapeutic promise of immune checkpoint inhibito

Inflammatory Pathophysiology as a Contributor to Myeloproliferative Neoplasms.

Myeloid neoplasms, including acute myeloid leukemia (AML), myeloproliferative neoplasms (MPNs), and myelodysplastic syndromes (MDS), feature clonal dominance and remodeling of the bone marrow niche in a manner that promotes malignant over non-malignant hematopoiesis. This take-over of hematopoiesis by the malignant clone is hypothesized to include hyperactivation of inflammatory signaling and overproduction of inflammatory cytokines. In the Ph-negative MPNs, inflammatory cytokines are considered to be responsible for a highly deleterious pathophysiologic process: the phenotypic transformation

Tumor angiogenesis as a target for dietary cancer prevention.

Between 2000 and 2050, the number of new cancer patients diagnosed annually is expected to double, with an accompanying increase in treatment costs of more than $80 billion over just the next decade. Efficacious strategies for cancer prevention will therefore be vital for improving patients' quality of life and reducing healthcare costs. Judah Folkman first proposed antiangiogenesis as a strategy for preventing dormant microtumors from progressing to invasive cancer. Although antiangiogenic drugs are now available for many advanced malignancies (colorectal, lung, breast, kidney, liver, brain,

Oral Communication abstracts

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Abstracts cont.

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Семья гистона деацетилазы в здравии и болезни.

Классические деацетилазы, включая классы I, II и IV, в зависимости от цинка, повсеместно присутствуют у млекопитающих и играют жизненно важную роль в многочисленных биологических процессах. На сегодняшний день eleven Были выявлены члены < < хисттон деацетилаза > > , а именно < < хиттон деацетилаза > > . 1 через гистонную деацетилазу 11. Растущий объем данных подчеркивает важнейшую роль этих гистоновых деацетилазов как в физиологических, так и патологических условиях. В частности, эти гистонные деацетилазы участвуют в различных клеточных процессах, включая воспаление, ме

Pulmonary origin and risk assessment of cancer-associated thrombosis.

Cancer-associated thrombosis (CAT) is a serious complication frequently observed in patients with cancer; however, its exact mechanism is not yet fully understood. Recent research in 2025 suggests that the lungs play a significant role in providing prothrombotic factors. Both primary and metastatic lung tumors have the potential to induce a state of hypercoagulability through various pathways, such as the secretion of procoagulant molecules, such as tissue factor (TF), triggering local inflammatory responses, platelet activation, and alterations in the function of vascular endothelial cells. F

LncRNA NEAT1 restrains the malignant biological characteristics of acute myeloid leukemia via regulating CTCF/CXCR2 axis.

Acute myeloid leukemia (AML) is notorious in the field of hematology for its poor efficacy, frustrating prognosis, and it is prone to refractory or relapsed conditions. Previous studies in our team have shown that some Long noncoding RNAs (lncRNAs) and chemokine receptors play key regulatory roles in AML. The findings of this study demonstrated that the expression of NEAT1 was atypically low in both clinical AML specimens and AML cell lines. Overexpression of NEAT1 was capable of attenuating the malignant biological characteristics of AML cells, including inhibiting the malignant proliferation

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… Liu Y Liu G Targeting NEAT1 affects the sensitivity to PARPi in serous ovarian cancer by regulating the homologous recombination repair pathway J Cancer 2024 15 5 1397 413 10.7150/jca.91896 38356722 PMC10861825 Liu Y, Liu G. … Targeting NEAT1 affects the sensitivity to PARPi in serous ovarian cancer by regulating the homologous recombination repair pathway. J Cancer. 2024;15(5):1397–413. 10.7150/jca.91896. 38356722 10.7150/jca.91896 PMC10861825 45. …

Molecular-Based Treatment Strategies for Osteoporosis: A Literature Review.

Osteoporosis is an unavoidable public health problem in an aging or aged society. Anti-resorptive agents (calcitonin, estrogen, and selective estrogen-receptor modulators, bisphosphonates, anti-receptor activator of nuclear factor κB ligand antibody along with calcium and vitamin D supplementations) and anabolic agents (parathyroid hormone and related peptide analogs, sclerostin inhibitors) have major roles in current treatment regimens and are used alone or in combination based on the pathological condition. Recent advancements in the molecular understanding of bone metabolism and in bioengin

MicroRNAs in B-cells: from normal differentiation to treatment of malignancies.

MicroRNAs (miRNAs) are small non-coding RNAs that play important post-transcriptional regulatory roles in a wide range of biological processes. They are fundamental to the normal development of cells, and evidence suggests that the deregulation of specific miRNAs is involved in malignant transformation due to their function as oncogenes or tumor suppressors. We know that miRNAs are involved in the development of normal B-cells and that different B-cell subsets express specific miRNA profiles according to their degree of differentiation. B-cell-derived malignancies contain transcription signatu

Interpreting clinical assays for histone deacetylase inhibitors.

As opposed to genetics, dealing with gene expressions by direct DNA sequence modifications, the term epigenetics applies to all the external influences that target the chromatin structure of cells with impact on gene expression unrelated to the sequence coding of DNA itself. In normal cells, epigenetics modulates gene expression through all development steps. When "imprinted" early by the environment, epigenetic changes influence the organism at an early stage and can be transmitted to the progeny. Together with DNA sequence alterations, DNA aberrant cytosine methylation and microRNA deregulat

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… HDAC 10 and 9 are required for chromosome homologous recombination. 24 Class III HDACs include 7 different members of the sirtuin (SIRT) family. They are dependent on nicotinamine adenine dinucleotide (NAD+) to remove the acetyl group from lysine residues in histones and nonhistone substrates. … Kotian S Liyanarachchi S Zelent A Histone deacetylases 9 and 10 are required for homologous recombination J Biol Chem. Epub 2011 Jan 18. 10.1074/jbc.C110.194233 PMC3048658 21247901 25. …

Benzyl isothiocyanate suppresses development of thyroid carcinoma by regulating both autophagy and apoptosis pathway.

Anaplastic thyroid carcinoma (ATC) is the most aggressive type of thyroid cancer, characterized by rapid growth and invasion and poor prognosis. Due to its rarity and aggressive nature, ATC is a difficult condition to treat, thus knowledge of the mechanisms underlying its progression represents important research challenges. Benzyl isothiocyanate (BITC) is a natural compound that has shown promising anticancer properties. The aim of this study was to evaluate the antitumor effect of BITC in ATC, highlighting signaling pathways involved in BITC mechanism of action. This work included in vitro a

Chemotherapy Side-Effects: Not All DNA Damage Is Equal.

Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment and later in life they are frequently confronted with the severe negative side-effects of their life-saving treatment. The occurrence of numerous features of accelerated aging, seriously affecting quality of life, has now become one of the most pressing problems associated with (pediatric) cancer treatment. Chemotherapies frequently target and damage the DNA, causing mutations or genome instability, a major hallmark

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… These include amongst others homologous recombination (HR) and non-homologous end joining (NHEJ) for the repair of double-stranded DNA breaks [ 158 ], base excision repair (BER) for the removal of subtle base modifications [ 159 ], global genome-nucleotide excision repair (GG-NER) and transcription-coupled …

Effect of the BH3 Mimetic Polyphenol (-)-Gossypol (AT-101) on the in vitro and in vivo Growth of Malignant Mesothelioma.

Malignant mesothelioma (MM) is a primary tumor arising from mesothelial cells. The survival of MM patients following traditional chemotherapy is poor, thus innovative treatments for MM are needed. (-)-gossypol (AT-101) is a BH3 mimetic compound which possesses anti-tumoral activity by targeting multiple signaling transduction pathways. Several clinical trials employing AT-101 have been performed and some of them are still ongoing. Accordingly, we investigated the in vitro effects of AT-101 on cell proliferation, cell cycle regulation, pro-survival signaling pathways, apoptosis and autophagy of

Update on the treatment of cutaneous T-cell lymphoma (CTCL): Focus on vorinostat.

Epigenetic regulation of gene transcription by small molecule inhibitors of histone deacetylases (HDAC) is a novel cancer therapy. Vorinostat (Zolinza()) is the first FDA approved HDAC-inhibitor for treatment of patients with cutaneous T cell lymphoma (CTCL) who have progressive, persistent or recurrent disease on or following two systemic therapies. Vorinostat was active against solid tumors and hematologic malignancies as intravenous and oral preparations in Phase I development. In two Phase II trials, vorinostat was safe and effective at an oral dose of 400 mg/day with an overall response r

Клетки T-бет+CXCR3+B вызывают гиперреактивное взаимодействие клеток B-T в множестве склерозов.

Множественный склероз (MS) — аутоиммунное заболевание центральной нервной системы (CNS). Одним из ключевых механизмов в НР является автораспространение (АП) ячеек В и Т, основанное на самопропитании. Здесь мы показываем, что про-воспаление B-T-обогащенные клетки клеток (BTEC) формируются во время AP и зеркальные особенности реакции микроцентра. T-bet+CXCR3+B — основной подмножество клеток, усиливающих и поддерживающих свои параллельные клетки TH1 с помощью интерферона (IFN)-__, и присутствуют в сильно воспламенённой менингетной ткани. Фундаментальная сигнатура активации клеток В находит свое о

Dying of Stress: Chemotherapy, Radiotherapy, and Small-Molecule Inhibitors in Immunogenic Cell Death and Immunogenic Modulation.

Innovative strategies to re-establish the immune-mediated destruction of malignant cells is paramount to the success of anti-cancer therapy. Accumulating evidence suggests that radiotherapy and select chemotherapeutic drugs and small molecule inhibitors induce immunogenic cell stress on tumors that results in improved immune recognition and targeting of the malignant cells. Through immunogenic cell death, which entails the release of antigens and danger signals, and immunogenic modulation, wherein the phenotype of stressed cells is altered to become more susceptible to immune attack, radiother

Emergence of immunotherapy as a novel way to treat hepatocellular carcinoma.

Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen presenting cells (APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor immunity is frequently repressed at tumor sites. Malignantly transformed cells rarely survive the attack by the immune system, but cells that do survive change their phenotypes to reduce their immunogenicity. The resultant cells evade the attack by the immune system and form clinically discernible tumors. Tumor microenvironments simultaneously contain a wide variety of immune suppre