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Recent advances in CAR-MSCs: the new engine of cellular immunotherapy evolution.

In recent years, the development of chimeric antigen receptor (CAR) technology has greatly promoted the progress of cellular immunotherapy. Among them, CAR-T cell therapy has shown remarkable clinical effects in the treatment of hematological malignancies. However, this therapy still faces a series of challenges, including immunogenicity, toxic side effects, and insufficient maintenance of long-term efficacy. The latest research progress has extended CAR technology to mesenchymal stem cells (MSCs), and the resulting CAR-MSCs combine the precise targeting ability of CAR molecules with the inher

Новые знания о генетической основе и транскриптомном освещении вирулентности в вариантах Pseudomonas shiringae pv. actinidiae.

Псевдомонас сирингаэ pv. actindiae (Psa) является причинным агентом киви бактериального канцера, но факторы, влияющие на его патогенность в природных условиях, остаются малоизученными. В этом исследовании мы изолировали two Пса, штаммы G126 и G282, из зараженных киви садов в китайской провинции Гуйчжоу. Оба изолируют, отнесенные к категории Psa-biovar 3, были подтверждены через Psa3-specific и филогеномический анализ. Анализы патогенности на киви-фруктовых листьях и ветках «Хонгян» показали значительное сокращение числа некротических пятен и уменьшение размеров повреждений при инфекции G282 по

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… However, Psa3 isolated from cultivated Actinida arguta in New Zealand was linked with recombination between IS630 transposases and conserved mobile elements, especially the Tn 6212-encoded LysR regulator, which has global effects on chromosomal gene expression [ 18 , 20 ]. … Notably, YXH1 harbored 586 strain-specific genes, predominantly transposases, which were identifiable in its complete genome assembly but absent in draft-quality genomes of other strains (Figure S2B). …

Epigenetic Modifiers: Exploring the Roles of Histone Methyltransferases and Demethylases in Cancer and Neurodegeneration.

Histone methyltransferases (HMTs) and histone demethylases (HDMs) are critical enzymes that regulate chromatin dynamics and gene expression through the addition and removal of methyl groups on histone proteins. HMTs, such as PRC2 and SETD2, are involved in the trimethylation of histone H3 at lysine 27 and lysine 36, influencing gene silencing and activation. Dysregulation of these enzymes often leads to abnormal gene expression and contributes to tumorigenesis. In contrast, HDMs including KDM7A and KDM2A reverse these methylation marks, and their dysfunction can drive disease progression. In c

Functional Investigation of IGF1R Mutations in Multiple Myeloma.

High expression of the receptor tyrosine kinase (RTK) insulin-like growth factor-1 receptor (IGF1R) and RTK mutations are associated with high-risk/worse prognosis in multiple myeloma (MM). Combining the pIGF1R/pINSR inhibitor linsitinib with the proteasome inhibitor (PI) bortezomib seemed promising in a clinical trial, but IGF1R expression was not associated with therapy response. Because the oncogenic impact of IGF1R mutations is so far unknown, we investigated the functional impact of IGF1R mutations on survival signaling, viability/proliferation and survival response to therapy. We transfe

Challenges and new technologies in adoptive cell therapy.

Adoptive cell therapies (ACTs) have existed for decades. From the initial infusion of tumor-infiltrating lymphocytes to the subsequent specific enhanced T cell receptor (TCR)-T and chimeric antigen receptor (CAR)-T cell therapies, many novel strategies for cancer treatment have been developed. Owing to its promising outcomes, CAR-T cell therapy has revolutionized the field of ACTs, particularly for hematologic malignancies. Despite these advances, CAR-T cell therapy still has limitations in both autologous and allogeneic settings, including practicality and toxicity issues. To overcome these c

SLAMF7: A Potential Target for CAR T-Cell Therapy in Multiple Myeloma.

Signaling Lymphocyte Activation Molecule Family member 7 (SLAMF7) represents a potential target for CAR T-cell therapy in the treatment of multiple myeloma (MM), and it is a promising alternative to classic BCMA-CAR therapy. The receptor is expressed on immune cells, particularly natural killer cells and T cells, that can trigger both activating and inhibitory signals. It is highly expressed in MM cells at all disease stages, playing a crucial role in cell adhesion and communication between immune cells, and being involved in the development and progression of the disease. The target has a pro

Therapeutic Potential of CAR-CIK Cells in Acute Leukemia Relapsed Post Allogeneic Stem Cell Transplantation.

Adoptive cellular therapy with donor-derived T cells has always been an attractive strategy after allogeneic hematopoietic stem cell transplantation (allo-HSCT) to reduce the risk of relapse in acute myeloid and lymphoid leukemias. Donor lymphocyte infusion (DLI) is still the best-established option, especially in the preemptive phase when measurable residual disease (MRD) becomes positive and in the prophylactic setting-when MRD is not detectable. However, the clinical benefit of DLI is counterbalanced by the possible onset of graft-versus-host disease (GvHD), which continues to restrict its

Cancer immunotherapy insights: key takeaways from the ADSCC bone marrow and cellular therapy congress 2024.

The rising global cancer burden underscores the urgent need for innovative and effective therapies. Molecular and cellular immunology advances have revolutionized cancer immunotherapy, transforming laboratory discoveries into clinical breakthroughs. The Second Bone Marrow Transplant and Cellular Therapy Congress, held in Abu Dhabi, United Arab Emirates (UAE), on October 26th - 27th, 2024, and sponsored by the Abu Dhabi Stem Cells Center (ADSCC), convened global experts to discuss cutting-edge developments in adoptive cell transfer (ACT); chimeric antigen receptor T-cell (CAR-T) therapy, tumor-

Advances in improving cancer immunotherapy with nanotechnology: from smart nanoparticles to synergistic combination strategies.

Cancer immunotherapy has substantially advanced cancer treatment, achieving durable responses in select malignancies. However, its widespread application is limited by significant challenges: low efficacy in many solid tumors, severe side effects, and immune evasion facilitated by the tumor microenvironment (TME). Nanotechnology offers a promising approach to address these obstacles. By employing nanoparticles (NPs), we can precisely deliver therapeutics to tumor sites, ensure controlled release to minimize side effects, and amplify the immune response, thereby substantially boosting the effec

Overhauling CAR T Cells to Improve Efficacy, Safety and Cost.

Gene therapy is now surpassing 30 years of clinical experience and in that time a variety of approaches has been applied for the treatment of a wide range of pathologies. While the promise of gene therapy was over-stated in the 1990's, the following decades were met with polar extremes between demonstrable success and devastating setbacks. Currently, the field of gene therapy is enjoying the rewards of overcoming the hurdles that come with turning new ideas into safe and reliable treatments, including for cancer. Among these modalities, the modification of T cells with chimeric antigen recepto

CAR-T-Cell-Based Cancer Immunotherapies: Potentials, Limitations, and Future Prospects.

Cancer encompasses various elements occurring at the cellular and genetic levels, necessitating an immunotherapy capable of efficiently addressing both aspects. T cells can combat cancer cells by specifically recognizing antigens on them. This innate capability of T cells has been used to develop cellular immunotherapies, but most of them can only target antigens through major histocompatibility complexes (MHCs). New gene-editing techniques such as clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (CRISPR-cas9) can precisely edit the DNA sequences. CRISPR-c

Scientific Advancements in Gene Therapies: Opportunities for Global Regulatory Convergence.

On 4 September 2024, the Reagan-Udall Foundation for the FDA (FDA Foundation) in collaboration with the Food and Drug Administration (FDA) and the Gates Foundation hosted a workshop titled "Scientific Advancements in Gene Therapies: Opportunities for Global Regulatory Convergence". The event brought together a diverse group of experts, including international regulatory bodies, regulated industries, healthcare professionals, patients, academic researchers and global health advocates, to discuss the rapid advancements in gene therapy and the pressing need for equitable access in low-and middle-

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… Genome editing with CRISPR-Cas nucleases, base editors, transposases and prime editors. Nat. Biotechnol. 2020;38:824–844. doi: 10.1038/s41587-020-0561-9. 16. Gaudelli N., Komor A., Rees H.A., Packer M.S., Badran A.H., Bryson D.I., Liu D.R. …

Миксобактериальная реакция на воздействие метильясмоната свидетельствует о вкладе в набор микропрепараторов на заводы.

Химические обмены между растениями и микробами в пределах ризобиомы имеют решающее значение для развития общинной структуры. Такие летучие корневые экюды, как фитохормоновый метилжасмонат (MeJA), способствуют принятию различных мер реагирования в связи со стрессом на растения, и они были причастны к тому, чтобы играть определенную роль в поддержании микробных сообществ. Миксобактерия является компетентным хищником растительных патогенов и, как правило, считается полезной для ризобиомов. Хотя было предложено использовать миксобактерию растений для защиты от патогенов, не известно о каких-либо с

Chimeric Antigen Receptors Based on Low Affinity Mutants of FcεRI Re-direct T Cell Specificity to Cells Expressing Membrane IgE.

IgE is the key mediator of allergic responses. Omalizumab, an IgE-specific monoclonal antibody that depletes IgE, is effective for treating severe allergic asthma. The need for frequent administration of the expensive drug, however, limits its applications. Taking advantage of T cell memory, adoptive T cell therapy (ACT) targeting IgE-producing cells has the potential to achieve long-term suppression of IgE and relief of symptoms for severe allergic diseases. The transmembrane form of IgE (mIgE), which is present on all IgE-producing cells, serves as an excellent molecular target for ACT that

GZMK-expressing CD8+ T cells promote recurrent airway inflammatory diseases.

Inflammatory diseases are often chronic and recurrent, and current treatments do not typically remove underlying disease drivers1. T cells participate in a wide range of inflammatory diseases such as psoriasis2, Crohn's disease3, oesophagitis4 and multiple sclerosis5,6, and clonally expanded antigen-specific T cells may contribute to disease chronicity and recurrence, in part by forming persistent pathogenic memory. Chronic rhinosinusitis and asthma are inflammatory airway diseases that often present as comorbidities7. Chronic rhinosinusitis affects more than 10% of the general population8. Am

Репрессии на цикле синергии со стороны HDAC/EZH2 H3K27-altered диффузная средняя глиома.

Diffuse midline glioma (DMG) — агрессивная хитрость под воздействием H3K27M онкохистоуна, приводящая к глобальному эпигенетическому регулированию и ограниченной эффективности одноагентной эпигенетической терапии. Ранее мы наблюдали клиническую выгоду от ингибитора HDAC/EZH2, но механистическая основа была неясной. Для принятия ответных мер в связи с наркотиками и проведения функциональных анализов использовалась группа культур ДИМ-глиомы стволовых клеток (ГНК) от опухолей головного мозга и спинного мозга, при этом репрезентативные модели были дополнительно проанализированы на предмет транскрип

Allogeneic and other innovative chimeric antigen receptor platforms.

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Balancing Quality, Cost, and Access During Delivery of Newer Cellular and Immunotherapy Treatments.

Purpose of reviewThe chimeric antigen receptor (CAR) T-cell therapy is currently changing the landscape of hematologic malignancies with multiple FDA-approved cell therapy products in the USA. The current administration process of the CAR T-cell therapy is complicated, labor-intensive, and expensive.Recent findingsThe chimeric antigen receptor (CAR) T-cell therapy is currently changing the landscape of hematologic malignancies with multiple FDA-approved cell therapy products in the USA. The current administration process of the CAR T-cell therapy is complicated, labor-intensive, and expensive.

Application of single-cell and spatial omics in deciphering cellular hallmarks of cancer drug response and resistance.

Drug resistance poses a significant challenge in cancer therapy, contributing to rapid recurrence, disease progression, and high patient mortality. Despite its critical impact, few reliable predictors for cancer drug response or failure have been established for clinical application. Tumor heterogeneity and the tumor microenvironment (TME) are pivotal factors influencing cancer drug efficacy and resistance. Tumor heterogeneity leads to variable therapeutic responses among patients, while dynamic interactions between cancer cells and the TME enhance tumor survival and proliferation, underscorin

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… sequencing depth, inadequate transcript coverage, technical noise, limited spatial resolution, sampling bias, RNA quality issues, amplification bias, batch effects | Studies of the immune microenvironment, developmental trajectories, and cellular heterogeneity | [ 27 , 28 ] Single-cell epigenomics | Transposase … Among these, scATAC-seq can reveal differences in chromatin status and function among various cells by combining single-cell sequencing with transposases. …

The Role of Drug Repurposing in the Development of Novel Antimicrobial Drugs: Non-Antibiotic Pharmacological Agents as Quorum Sensing-Inhibitors.

Background: The emergence of multidrug-resistant organisms (MDROs) is a global public health issue, severely hindering clinicians in administering appropriate antimicrobial therapy. Drug repurposing is a drug development strategy, during which new pharmacological applications are identified for already approved drugs. From the viewpoint of the development of virulence inhibitors, inhibition of quorum sensing (QS) is a promising route because various important features in bacterial physiology and virulence are mediated by QS-dependent gene expression. Methods: Forty-five pharmacological agents,