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Инженерный антитела TACI × CD3 для перенаправления Т клеток на множественные миэломы.

Вышеупомянутые аббревиатуры, предназначенные для антигена созревания клеток В (BCMA), являющегося членом сверхсемейства суперрецептора некроза опухоли (TNFR), продемонстрировали замечательную клиническую эффективность в лечении рецидива/рефрактора множественной миеломы (MM). Вместе с тем одной из серьезных проблем является частое снижение регулирования или потеря выражения БКМА у пациентов, получающих иммунотерапию, ориентированную на БКМА, что существенно снижает терапевтическую эффективность и способствует прогрессированию и устойчивости к заболеваниям после первоначальной позитивной реакции

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… Similarly, it bound CD3 on Jurkat cells above 0.3nM but showed no binding to CD3 − K562 cells at even 10nM. These results confirm that the TACI × CD3 bsAb retains integrity and dual binding specificity for TACI and CD3. …

Dibromo-Edaravone Induces Anti-Erythroleukemia Effects via the JAK2-STAT3 Signaling Pathway.

Acute erythroid leukemia (AEL) is a rare and aggressive hematological malignancy managed with chemotherapy, targeted therapies, and stem cell transplantation. However, these treatments often suffer from limitations such as refractoriness, high toxicity, recurrence, and drug resistance, underscoring the urgent need for novel therapeutic approaches. Dibromo-edaravone (D-EDA) is a synthetic derivative of edaravone (EDA) with unreported anti-leukemic properties. In this study, D-EDA demonstrated potent cytotoxicity against HEL cells with an IC50 value of 8.17 ± 0.43 μM using an MTT assay. Morpholo

Изучение связи между ядерными рецепторами в гематологических галереях.

Гематологические магнации (ГМ) представляют собой подмножество новообразований, затрагивающих кровь, костный мозг и лимфатические системы, которые в основном подразделяются на лейкемию, лимфому и множественную миелому. Их прогнозы значительно отличаются друг от друга, причем, несмотря на текущее лечение, часто возникает опасность рецидива. Несмотря на то, что современные терапевтические стратегии расширили общее выживание пациентов, они не предлагают лечения на продвинутых этапах и часто приводят к таким проблемам, как приобретение лекарственной устойчивости, рецидивы и серьезные побочные эффе

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… cells | DIM #34 B | ↑ cleaved Caspase-3, -9 | [ 85 ] | In vitro | HL-60 cells | DIM #34 B | ↑ Apoptosis | [ 85 ] | In vitro | U937 cells | DIM#34 B + LG100268 , DIM#34 B + LG100069 , DIM#34 B + ATRA | ↑ Apoptosis | [ 85 ] | In vitro | Jurkat cells | 15d-PGJ2 A | ↑ DR5, TRAIL induced apoptosis | [ … 86 ] | In vitro | EoL-1, U937, KPB-M15 cells | Troglitazone A | ↑ p21 ↓ Cell proliferation | [ 87 ] | In vitro | EoL-1 cells | Troglitazone A | ↑ Cells arrest, G0/G1 phase population | [ 87 ] | In vitro | CLL cells, Jurkat cells | CDDO A | ↑ Apoptosis | [ 88 ] | In vitro | HL-60 cells | Troglitazone …

New light on chemotherapy toxicity and its prevention.

Most patients with cancer receive chemotherapy. Unfortunately, chemotherapy is associated with a number of potentially life-threatening side effects. There is a need to ameliorate chemotoxicity to improve therapeutic outcomes and quality of life. Chemotoxicity arises from systemic DNA damage and inflammation in healthy cells due to chemotherapy drugs. Traditionally, these processes are believed to be caused by the direct death of normal cells by chemotherapeutic drugs. However, new research has challenged this dogma by suggesting that chemotoxicity is a secondary effect associated with the rel

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… When experiments in the same study were performed using dead Jurkat cells that had been pre-labelled with the thymidine analogue bromodeoxyuridine (BrdU) prior to Adriamycin treatment, numerous BrdU-labelled fluorescent particles representing DNA were found to have accumulated in the nuclei of NIH3T3 … This indicated the involvement of cfChPs released from dying Jurkat cells in the aforementioned bystander effect. The phenomenon of chemotherapy-induced bystander effect is pictorially depicted in Fig. 1 . …

A Novel Bispecific T-Cell Engager (CD1a x CD3ε) BTCE Is Effective against Cortical-Derived T Cell Acute Lymphoblastic Leukemia (T-ALL) Cells.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy burdened by poor prognosis. While huge progress of immunotherapy has recently improved the outcome of B-cell malignancies, the lack of tumor-restricted T-cell antigens still hampers its progress in T-ALL. Therefore, innovative immunotherapeutic agents are eagerly awaited. To this end, we generated a novel asymmetric (2 + 1) bispecific T-cell engager (BTCE) targeting CD1a and CD3ε (CD1a x CD3ε) starting from the development of a novel mAb named UMG2. UMG2 mAb reacts against CD1a, a glycoprotein highly expressed by cortical

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… Jurkat cells were co-cultured at 10.1 E:T ratio with undepleted PBMCs, CD56 depleted, total PBMCs exposed to Fc blocker, or only CD56+ lymphocytes. … Expression of exhaustion markers (PD-1, TIM-3, LAG-3, and TIGIT) on CD4+ and CD8+ T-lymphocytes co-cultured with Jurkat cell line in the presence of CD1a x CD3 alone, CD1a x CD3ε plus anti-PD-1, or anti PD-L1. * p < 0.05, ** p < 0.01. 4. …

Influence of Metamizole on Antitumour Activity of Risedronate Sodium in In Vitro Studies on Canine (D-17) and Human (U-2 OS) Osteosarcoma Cell Lines.

The availability of metamizole varies greatly around the world. There are countries such as the USA, UK, or Australia where the use of metamizole is completely forbidden, and there are also countries where this drug is available only on prescription (e.g., Greece, Italy, Spain, etc.) and those in which it is sold OTC-over the counter (e.g., most Asian and South American countries). Metamizole, as a drug with a strong analgesic effect, is used as an alternative to other non-steroidal anti-inflammatory drugs, alone or in combination with opioid drugs. Risedronate sodium is a third-generation bis

Parthenolide: pioneering new frontiers in hematological malignancies.

Hematological malignancies are the fifth most prevalent cancer category in developed countries, presenting significant treatment challenges. The side effects of chemotherapy and its non-selective nature have led researchers to explore combination therapies to enhance efficacy and improve patient outcomes. Parthenolide (PTL) emerges as a promising candidate, being the first small molecule identified for its selective action against leukemic stem cells. This article provides an overview of PTL's effects and its potential as a complementary treatment for hematological malignancies. A systematic s

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… PTL demonstrates cytotoxic and apoptotic activity against Jurkat cells as T-cell ALL, with an IC50 of 16.1 μM ( Mehri et al., 2020 ). … Osteopontin siRNA does not confer resistance to toxic effects of parthenolide in Jurkat cells . Exp. Oncol. 42 ( 3 ), 188 – 191 . 10.32471/exp-oncology.2312-8852.vol-42-no-3.15180 32996731 Minhajuddin M. Pei S. Ashton J. M. Callahan K. Lagadinou E. Balys M. ( 2011 ). …

Revisiting Proteasome Inhibitors: Molecular Underpinnings of Their Development, Mechanisms of Resistance and Strategies to Overcome Anti-Cancer Drug Resistance.

Proteasome inhibitors have shown relevant clinical activity in several hematological malignancies, namely in multiple myeloma and mantle cell lymphoma, improving patient outcomes such as survival and quality of life, when compared with other therapies. However, initial response to the therapy is a challenge as most patients show an innate resistance to proteasome inhibitors, and those that respond to the therapy usually develop late relapses suggesting the development of acquired resistance. The mechanisms of resistance to proteasome inhibition are still controversial and scarce in the literat

Promising Activities of Marine Natural Products against Hematopoietic Malignancies.

According to the WHO classification of tumors, more than 150 typologies of hematopoietic and lymphoid tumors exist, and most of them remain incurable diseases that require innovative approaches to improve therapeutic outcome and avoid side effects. Marine organisms represent a reservoir of novel bioactive metabolites, but they are still less studied compared to their terrestrial counterparts. This review is focused on marine natural products with anticancer activity against hematological tumors, highlighting recent advances and possible perspectives. Until now, there are five commercially avai

A phase 2 and pharmacological study of sapanisertib in patients with relapsed and/or refractory acute lymphoblastic leukemia.

BACKGROUND: Despite recent approval of several new agents, relapsed acute lymphoblastic leukemia (ALL) remains challenging to treat. Sapanisertib (MLN0128/TAK-228) is an oral TORC1/2 inhibitor that exhibited preclinical activity against ALL. METHODS: We conducted a single-arm multi-center Phase II study of sapanisertib monotherapy (3 mg orally daily of the milled formulation for 21 days every 28 days) in patients with ALL through the Experimental Therapeutics Clinical Trials Network (NCI-9775). RESULTS: Sixteen patients, 15 of whom were previously treated (median 3 prior lines of therapy), w

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… (A) Log phase Jurkat cells were treated for 24 h with diluent (0.1% DMSO, lane 1) or sapanisertib at the indicated concentration, lysed, and subjected to immunoblotting for phospho‐Thr 36 , 45 ‐4EBP1 or total 4EBP1. … Jurkat cells (lane 12) were included in the blot because they were known to be positive for all analytes. 29 The housekeeping protein nucleolin (NCL) served as a loading control. …

PARP Inhibitors and Haematological Malignancies-Friend or Foe?

Since their introduction several years ago, poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have become the standard of care for breast and gynaecological cancers with BRCA gene mutations. Given that PARPi act by exploiting defective DNA repair mechanisms within tumour cells, they should be ideally suited to combatting haematological malignancies where these pathways are notoriously defective, even though BRCA mutations are rare. To date, despite promising results in vitro, few clinical trials in humans for haematological malignancies have been performed, and additional investigation is

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… While PJ34 treatment did not induce apoptosis in MOLT4 or Jurkat cells in vitro [ 42 , 43 ], it induced apoptosis in human T-cell leukaemia virus type 1 (HTLV-1) transformed and a panel of patient-derived T-ALL cell lines in vitro [ 41 ]. … By contrast, combination of PJ34 and the NOTCH inhibitor (N-[N[(3,5-difluorophenacetyl)-l-alanyl]- S -phenylglycine t -butyl ester) (DAPT), or PJ34 and doxorubicin, etoposide, cytarabine, or chlorambucil, did not enhance the cytotoxicity of either drug in Jurkat cells in vitro [ 43 , 49 ]. …

An understanding of mitochondria and its role in targeting nanocarriers for diagnosis and treatment of cancer.

Nanotechnology has changed the entire paradigm of drug targeting and has shown tremendous potential in the area of cancer therapy due to its specificity. In cancer, several targets have been explored which could be utilized for the better treatment of disease. Mitochondria, the so-called powerhouse of cell, portrays significant role in the survival and death of cells, and has emerged as potential target for cancer therapy. Direct targeting and nanotechnology based approaches can be tailor-made to target mitochondria and thus improve the survival rate of patients suffering from cancer. With thi

Voltage-gated sodium channel as a target for metastatic risk reduction with re-purposed drugs.

ObjectiveTo determine the exact role of sodium channel proteins in migration, invasion and metastasis and understand the possible anti-invasion and anti-metastatic activity of repurposed drugs with voltage gated sodium channel blocking properties.Material and methodsA review of the published medical literature was performed searching for pharmaceuticals used in daily practice, with inhibitory activity on voltage gated sodium channels. For every drug found, the literature was reviewed in order to define if it may act against cancer cells as an anti-invasion and anti-metastatic agent and if it w

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… T lymphocytes (Jurkat cells) | Fraser, 2004 30 | Jurkat cells express VGSC and this protein has an important role in invasiveness of these cells. Pancreatic cancer cells | Sato K, 1994 31 | MIA-PaCa-2 and CAV cells were tested in vitro and in vivo with phenytoin (PHEN). …

Carfilzomib: a novel treatment in relapsed and refractory multiple myeloma.

Carfilzomib is a second-generation proteasome inhibitor with well-documented clinical activity as a single agent in patients with relapsed/refractory multiple myeloma. Carfilzomib can partially overcome resistance in bortezomib-refractory patients and has significant efficacy in bortezomib-naïve patients. Responses generally occur rapidly and are durable in the majority of cases. Carfilzomib can be safely administered in patients with renal failure and adverse cytogenetics do not seem to interfere with its activity. Moreover, carfilzomib has the advantage of a favorable safety profile, especia

Interleukin-32: a Pandora's box in human immunodeficiency virus infection.

Human immunodeficiency virus (HIV), which causes acquired immunodeficiency syndrome (AIDS), has been estimated to infect around 40.8 million people globally. This virus can persist and thrive in the presence of antiretroviral therapy, which is a major obstacle to HIV eradication. Therefore, understanding host immunological factors that underlie HIV persistence and pathogenesis can lead to the development of immunotherapeutic interventions. Interleukin-32 (IL-32) is an orphan cytokine with multiple isoforms and a complex signal transduction pathway that transmits through non-specific receptors.

Bispecific and multispecific T-cell engagers: advancing the future of immunotherapy.

T-cell engagers (TCEs) represent an emerging class of immunotherapies that harness T cells' cytotoxic power to eliminate diseased cells-a transformative future therapeutic strategy. TCEs form immunological synapses to trigger potent immune responses, with proven efficacy in blood cancers; research expands their use to solid tumors via innovative molecular design and improved safety profiles. Beyond oncology, TCEs hold promise in autoimmune disorders by eliminating autoreactive cells, offering novel avenues for diseases like lupus. However, achieving optimal outcomes without disrupting immune h

Antidepressant Drug Sertraline against Human Cancer Cells.

The use of FDA-approved drugs for new indications represents a faster and more economical way to find novel therapeutic agents for cancer therapy, compared to the development of new drugs. Repurposing drugs is advantageous in a pharmacological context since these drugs already have extensive data related to their pharmacokinetics, facilitating their approval process for different diseases. Several studies have reported the promising anticancer effects of sertraline, both alone and combined, in different types of cancer cell lines. Here, we performed a literature review on the anticancer potent

Nanoparticle-based strategy in CAR-T cell immunotherapy: challenges, implications, and perspectives.

Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable progress in treating hematologic malignancies, yet its broader application faces challenges such as manufacturing complexity, solid tumor microenvironment barriers, and immune toxicity. Nanoparticles (NPs), leveraging their precise delivery, immunomodulation, and multifunctional integration capabilities, offer innovative strategies to optimize CAR-T cell therapy. This review provides a comprehensive elucidation of the fundamental framework of CAR-T cell therapy and the challenges in oncological applications. Subsequently, w

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… cells Primary human T cells Equivalent to electroporation Acute lymphoblastic leukemia [ 33 ] Lipid Nanoparticle CD19-targeted CAR mRNA Human T cells 22.6% Leukemia [ 80 ] Ionizable lipid nanoparticle CD19-targeted CAR mRNA Jurkat cells Primary human T cells B10 LNPs are comparable to electroporation … cells Primary human T cells | Equivalent to electroporation | Acute lymphoblastic leukemia | [ 33 ] Lipid Nanoparticle | CD19-targeted CAR mRNA | Human T cells | 22.6% | Leukemia | [ 80 ] Ionizable lipid nanoparticle | CD19-targeted CAR mRNA | Jurkat cells Primary human T cells | B10 LNPs are comparable …

The Role of the CREB Protein Family Members and the Related Transcription Factors in Radioresistance Mechanisms.

In the framework of space flight, the risk of radiation carcinogenesis is considered a "red" risk due to the high likelihood of occurrence as well as the high potential impact on the quality of life in terms of disease-free survival after space missions. The cyclic AMP response element-binding protein (CREB) is overexpressed both in haematological malignancies and solid tumours and its expression and function are modulated following irradiation. The CREB protein is a transcription factor and member of the CREB/activating transcription factor (ATF) family. As such, it has an essential role in a

Targeted CD7 CAR T-cells for treatment of T-Lymphocyte leukemia and lymphoma and acute myeloid leukemia: recent advances.

The high expression of CD7 targets in T-cell acute lymphoblastic leukemia (T-ALL) and T-lymphoma has attracted considerable attention from researchers. However, because CD7 chimeric antigen receptor (CAR) T-cells undergo fratricide, CD7 CAR T-cells develop an exhaustion phenotype that impairs the effect of CAR T-cells. There have been significant breakthroughs in CD7-targeted CAR T-cell therapy in the past few years. The advent of gene editing, protein blockers, and other approaches has effectively overcome the adverse effects of conventional methods of CD7 CAR T-cells. This review, in conjunc