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Adoptive Immunotherapy and High-Risk Myeloma.

Despite significant improvements in the treatment of multiple myeloma (MM), it remains mostly incurable, highlighting a need for new therapeutic approaches. Patients with high-risk disease characteristics have a particularly poor prognosis and limited response to current frontline therapies. The recent development of immunotherapeutic strategies, particularly T cell-based agents have changed the treatment landscape for patients with relapsed and refractory disease. Adoptive cellular therapies include chimeric antigen receptor (CAR) T cells, which have emerged as a highly promising therapy, par

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of hematologic malignancies: multiple myeloma, lymphoma, and acute leukemia.

Increasing knowledge concerning the biology of hematologic malignancies as well as the role of the immune system in the control of these diseases has led to the development and approval of immunotherapies that are resulting in impressive clinical responses. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a hematologic malignancy Cancer Immunotherapy Guidelines panel consisting of physicians, nurses, patient advocates, and patients to develop consensus recommendations for the clinical application of immunotherapy for patients with multiple myeloma, lymphoma, and acute leukemi

Rejuvenation Strategy for Inducing and Enhancing Autoimmune Response to Eliminate Senescent Cells.

The process of aging, which involves progressive changes in the body over time, is closely associated with the development of age-related diseases. Cellular senescence is a pivotal hallmark and mechanism of the aging process. The accumulation of senescent cells can significantly contribute to the onset of age-related diseases, thereby compromising overall health. Conversely, the elimination of senescent cells enhances the body's regenerative and reparative capacity, thereby retarding the aging process. Here, we present a brief overview of 12 Hallmarks of aging and subsequently emphasize the po

Cytokine Release Syndrome: Current Perspectives.

Chimeric antigen receptor T cell (CART) therapy represents a novel and a paradigm-shifting approach to treating cancer. Recent clinical successes have widened the applicability of CD19 CART cells for the treatment of relapsed/refractory B-cell NHL, namely tisagenleclucel and axicabtagene ciloleucel. Tisagenleclucel is also approved for relapsed and/or refractory B-ALL up to age 25. CART therapy is associated with unique and potentially life-threatening toxicities, notably cytokine release syndrome (CRS). A better understanding of the pathogenesis of CRS is crucial to ensure proper management.

Crosstalk of the Wnt/β-Catenin Signaling Pathway in the Induction of Apoptosis on Cancer Cells.

The Wnt/β-catenin signaling pathway plays a major role in cell survival and proliferation, as well as in angiogenesis, migration, invasion, metastasis, and stem cell renewal in various cancer types. However, the modulation (either up- or downregulation) of this pathway can inhibit cell proliferation and apoptosis both through β-catenin-dependent and independent mechanisms, and by crosstalk with other signaling pathways in a wide range of malignant tumors. Existing studies have reported conflicting results, indicating that the Wnt signaling can have both oncogenic and tumor-suppressing roles, d

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… The DISC-FADD complex binds initiator caspases like caspase-8 and -10 through their death effector domain (DED), causing the autocatalytic cleavage of procaspase-8. The activated caspase-8, in turn, activates executioner caspases (caspase-3 and -7). … effector domain | DED Death-inducing signaling complex | DISC Deoxyribonucleic acid | DNA Docosahexaenoic acid | DHA Element-binding protein | CBP Epidermal growth factor receptor | EGFR Extracellular-signal-regulated kinase | ERK Fas-associated death domain-containing | FADD Forkhead box class O | …

Potential Immunotherapy Targets for Liver-Directed Therapies, and the Current Scope of Immunotherapeutics for Liver-Related Malignancies.

Liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, is increasing in incidence and mortality across the globe. An improved understanding of the complex tumor microenvironment has opened many therapeutic doors and led to the development of novel pharmaceuticals targeting cellular signaling pathways or immune checkpoints. These interventions have significantly improved tumor control rates and patient outcomes, both in clinical trials and in real-world practice. Interventional radiologists play an important role in the multidisciplinary team given their expertise

Application of GPRC5D Targeting Therapy in Relapsed Refractory Multiple Myeloma.

BackgroundAs a rapidly developing therapeutic method, targeted therapy plays an important role in the treatment of multiple myeloma. In recent years, mature B cell antigen-targeting therapy has brought new hope for patients with refractory/relapsed disease. While an increasing number of patients with relapse are exposed to this type of drug, changing the therapeutic target may be an effective strategy for patients with relapse/refractory multiple myeloma.ObjectivesThe expression of G protein-coupled receptor, class C Group 5 member D (GPRC5D), on the surface of myeloma tumor cells makes it a p

Advancing CAR-NK cell therapy in solid tumors: Current landscape and future directions.

Chimeric antigen receptor (CAR)-engineered natural killer (NK) cells have emerged as a promising modern immunotherapeutic strategy, offering advantages over CAR-T cell therapy due to their innate cytotoxicity, safety profile, and potential for scalable, off-the-shelf allogeneic manufacturing. CAR-NK cells can be generated from multiple sources, with recent clinical studies demonstrating notable efficacy and lack of severe toxicity in hematologic malignancies. Nevertheless, the translation of this success to solid tumors is hampered by limited NK cell persistence, trafficking and infiltration c

Chimeric antigen receptor (CAR) T therapies for the treatment of hematologic malignancies: clinical perspective and significance.

Chimeric Antigen Receptor (CAR) T cell therapies - adoptive T cell therapies that have been genetically engineered for a new antigen-specificity - have displayed significant success in treating patients with hematologic malignancies, leading to three recent US Food and Drug Administration approvals. Based on the promise generated from these successes, the field is rapidly evolving to include new disease indications and CAR designs, while simultaneously reviewing and optimizing toxicity and management protocols. As such, this review provides expert perspective on the significance and clinical c

Contemporary Monoclonal Antibody Utilization in Glomerular Diseases.

Therapeutic monoclonal antibodies (MAbs) have been one of the fastest growing drug classes in the past 2 decades and are indicated in the treatment of cancer, autoimmune disorders, solid organ transplantation, and glomerular diseases. The Food and Drug Administration has approved 100 MAbs between 1986 and 2021, and MAbs account for 20% of Food and Drug Administration's new drug approval every year. MAbs are preferred over traditional immunosuppressive agents because of their high specificity, reduced number of drug-drug interactions, and low toxicity, which make them a prime example of persona

Recent advances in adoptive cell therapy for cancer immunotherapy.

Adoptive cell therapy (ACT), a key direction in tumor immunotherapy, has achieved remarkable progress in recent years. This paper systematically reviews the current status and future trends of ACT, covering lymphokine-activated killer cells (LAK), tumor-infiltrating lymphocytes (TIL), cytokine-induced killer cells (CIK), dendritic cells (DC), T cell receptor-modified T cells (TCR-T), chimeric antigen receptor T cells (CAR-T), natural killer (NK) cells, chimeric antigen receptor-modified NK cells (CAR-NK), and the emerging CAR-M. The paper focuses on emerging technological approaches, including

Checkpoint inhibition and beyond: Precision immune engineering for the immune-privileged landscape of ocular malignancies.

Ocular malignancies, particularly uveal and conjunctival melanoma, exemplify tumors that evolve within one of the body's most immunologically constrained ecosystems, the eye's immune-privileged microenvironment. The limited success of PD-1/PD-L1 and CTLA-4 blockade in these cancers underscores the need to move beyond linear checkpoint inhibition toward multidimensional immune engineering. Through the confluence of synthetic bio-nanotechnology, AI-guided immunogenomics, and spatial immunomics, this review reframes ocular immunotherapy and redefines how tolerance and immunity might be programmat

Decoding the molecular mechanisms of pyroptosis and its therapeutic development prospects.

Pyroptosis is an emerging form of inflammatory programmed cell death primarily mediated by the gasdermin protein family, characterized by cell swelling, membrane pore formation, and the release of pro-inflammatory cytokines such as IL-1β and IL-18. This mode of cell death has garnered significant attention due to its critical involvement in a variety of diseases, including cancer, cardiovascular disorders, autoimmune diseases, and metabolic syndromes, positioning it as a promising therapeutic target. Despite advances, the complexity of pyroptosis regulation and its dual roles in disease pathog

Histone H3K18 Lactylation Promotes the Malignant Progression of Wilms Tumor via a PSRC1/AKT/HIF-1α Positive Feedback Loop.

Nephroblastoma, also known as Wilms tumor (WT), is the most common pediatric renal malignancy. Current treatment regimens exhibit limited efficacy in high-risk patients and are associated with long-term adverse effects. Through gene set enrichment analysis (GSEA) and validation using clinical specimens, we identified aberrant glycolytic activity in WT, which drives lactate accumulation. Lactate is not merely a metabolic byproduct but also a critical epigenetic regulator that mediates histone lactylation; however, its functional role in WT remains uncharacterized. In this study, we found that t

Antibodies to watch in 2025.

The commercial development of antibody therapeutics is a global enterprise involving thousands of biopharmaceutical firms and supporting service organizations. To date, their combined efforts have resulted in over 200 marketed antibody therapeutics and a pipeline of nearly 1,400 investigational product candidates that are undergoing evaluation in clinical studies as treatments for a wide variety of diseases. Here, we discuss key events in antibody therapeutics development that occurred during 2024 and forecast key events related to the late-stage clinical pipeline that may occur in 2025. In pa

Immunotherapy and CRISPR Cas Systems: Potential Cure of COVID-19?

The COVID-19 has plunged the world into a pandemic that affected millions. The continually emerging new variants of concern raise the question as to whether the existing vaccines will continue to provide sufficient protection for individuals from SARS-CoV-2 during natural infection. This narrative review aims to briefly outline various immunotherapeutic options and discuss the potential of clustered regularly interspaced short palindromic repeat (CRISPR Cas system technology against COVID-19 treatment as specific cure. As the development of vaccine, convalescent plasma, neutralizing antibodies

Application of Chimeric Antigen Receptor T Cells in the Treatment of Hematological Malignancies.

T cell immune protection plays a pivotal role in the treatment of patients with hematological malignancies. However, T cell exhaustion might lead to the possibility of immune escape of hematological malignancies. Adoptive cell therapy (ACT) with chimeric antigen receptor T (CAR-T) cells can restore the activity of exhausted T cell through reprogramming and is widely used in the treatment of relapsed/refractory (r/r) hematological malignancies. Of note, CD19, CD20, CD30, CD33, CD123, and CD269 as ideal targets have shown extraordinary potential for CAR-T cell therapy and other targets such as C

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

Precision in Action: The Role of Clustered Regularly Interspaced Short Palindromic Repeats/Cas in Gene Therapies.

Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-associated enzyme-CAS holds great promise for treating many uncured human diseases and illnesses by precisely correcting harmful point mutations and disrupting disease-causing genes. The recent Food and Drug Association (FDA) approval of the first CRISPR-based gene therapy for sickle cell anemia marks the beginning of a new era in gene editing. However, delivering CRISPR specifically into diseased cells in vivo is a significant challenge and an area of intense research. The identification of new CRISPR/Cas variants, particularly

Multiple Myeloma Therapy: Emerging Trends and Challenges.

Multiple myeloma (MM) is a complex hematologic malignancy characterized by the uncontrolled proliferation of clonal plasma cells in the bone marrow that secrete large amounts of immunoglobulins and other non-functional proteins. Despite decades of progress and several landmark therapeutic advancements, MM remains incurable in most cases. Standard of care frontline therapies have limited durable efficacy, with the majority of patients eventually relapsing, either early or later. Induced drug resistance via up-modulations of signaling cascades that circumvent the effect of drugs and the emergenc