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Revitalizing T cells: breakthroughs and challenges in overcoming T cell exhaustion.

T cell exhaustion is a prevalent phenomenon in chronic infections and tumor microenvironments, severely compromising the effectiveness of antitumor and antiviral immunity. In recent years, there has been significant progress in understanding the underlying mechanisms of T cell exhaustion, including external factors and intrinsic cellular changes that drive this dysfunctional state. Key external factors such as persistent antigen exposure, immune checkpoint signaling, and the cytokine milieu, as well as intrinsic changes such as altered metabolic processes, epigenetic modifications, and transcr

Cancer Vaccines and Beyond: The Transformative Role of Nanotechnology in Immunotherapy.

Cancer is one of the leading causes of morbidity and mortality globally, responsible for approximately 10 million deaths in 2022 and an estimated 21 million new cases in 2024. Traditional cancer treatments such as surgery, radiation therapy, and chemotherapy often present limitations in efficacy and side effects. However, immunotherapeutic vaccines have emerged as a promising approach, leveraging the body's immune system to target and eliminate cancer cells. This review examines the evolving landscape of cancer vaccines, differentiating between preventive and therapeutic strategies and highlig

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… Among them, adenoviruses stand out for being non-replicative, not causing disease in humans, and possessing a wide tissue tropism. …

"Bioinspired" Membrane-Coated Nanosystems in Cancer Theranostics: A Comprehensive Review.

Achieving precise cancer theranostics necessitates the rational design of smart nanosystems that ensure high biological safety and minimize non-specific interactions with normal tissues. In this regard, "bioinspired" membrane-coated nanosystems have emerged as a promising approach, providing a versatile platform for the development of next-generation smart nanosystems. This review article presents an in-depth investigation into the potential of these nanosystems for targeted cancer theranostics, encompassing key aspects such as cell membrane sources, isolation techniques, nanoparticle core sel

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… The tumor tropism of MSCs is also influenced by the presence of membrane proteins such as TGF-β, E-selectins, and P-selectins [ 48 ]. Since MSCs hardly express MHC molecules, their targeting mechanism is tumor-specific rather than species-specific. …

Immunotherapy in Multiple Myeloma.

Multiple myeloma is a complex disease and immune dysfunction has been known to play an important role in the disease pathogenesis, progression, and drug resistance. Recent efforts in drug development have been focused on immunotherapies to modify the MM disease process. Here, we summarize the emerging immunotherapies in the MM treatment landscape.

Molecular mechanisms and clinical management of cancer bone metastasis.

As one of the most common metastatic sites of malignancies, bone has a unique microenvironment that allows metastatic tumor cells to grow and flourish. The fenestrated capillaries in the bone, bone matrix, and bone cells, including osteoblasts and osteoclasts, together maintain the homeostasis of the bone microenvironment. In contrast, tumor-derived factors act on bone components, leading to subsequent bone resorption or excessive bone formation. The various pathways involved also provide multiple targets for therapeutic strategies against bone metastases. In this review, we summarize the curr

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… signaling may be used in combination with other therapies to induce sufficient suppression of tumor growth and spread. 460 Conclusion and perspective Bone metastasis is one of the most lethal complications of cancer, and further elucidation of this process should provide new insights into the bone tropism …

The Fifth International Meeting of ISEV, ISEV2016, Rotterdam, The Netherlands, 4 - 7 May, 2016.

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Целенаправленная деградация белка разрушает ненаркомные цели, чтобы обратить вспять иммунное уклонение и терапию устойчивости к раку.

Таргетированная деградация белков (ТД) использует эндогенные протеолитические системы — систему убиквина и протеасомы и лизосомальные пути — для селективного удаления белков, вызывающих болезни, которые не реагируют на традиционное ингибирование. В онкологической иммунотерапии ТД разрушает критические иммунодепрессивные узлы в экзоцитоплазматическом, мембранном и цитоплазматическом компартментах, перепрограммируя микросреду опухоли от иммунологически «холодной» к «горячей» состоянию. Эта статья рассматривает молекулярные принципы инженерии бифункциональных деградаторов и обобщает клинические д

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… On the other hand, strategies employing biological carriers—such as degradable platelets (DePLTs)—which covalently anchor protein of interest (POI) ligands to heat shock protein 90 (HSP90) within platelets, can exploit the natural tropism of platelets toward sites of hemorrhage to achieve targeted protein …

Emerging therapeutic strategies in glioblastsoma: drug repurposing, mechanisms of resistance, precision medicine, and technological innovations.

Glioblastoma (GBM) is an aggressive Grade IV brain tumor with a poor prognosis. It results from genetic mutations, epigenetic changes, and factors within the tumor microenvironment (TME). Traditional treatments like surgery, radiotherapy, and chemotherapy provide limited survival benefits due to the tumor's heterogeneity and resistance mechanisms. This review examines novel approaches for treating GBM, focusing on repurposing existing medications such as antipsychotics, antidepressants, and statins for their potential anti-GBM effects. Advances in molecular profiling, including next-generation

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… While some genetically modified OVs are engineered to enhance tumor specificity and therapeutic efficacy, others are naturally oncotropic, meaning they inherently exhibit tumor-selective tropism without genetic modification. …

Cell Therapy: Types, Regulation, and Clinical Benefits.

Cell therapy practices date back to the 19th century and continue to expand on investigational and investment grounds. Cell therapy includes stem cell- and non-stem cell-based, unicellular and multicellular therapies, with different immunophenotypic profiles, isolation techniques, mechanisms of action, and regulatory levels. Following the steps of their predecessor cell therapies that have become established or commercialized, investigational and premarket approval-exempt cell therapies continue to provide patients with promising therapeutic benefits in different disease areas. In this review

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… Albeit to a less documented extent compared to ACT products or other cellular therapies, genetically engineered MSCs have been investigated as a cancer treatment due to their ease of obtainment and demonstrated tumor tropism and anti-tumorigenic properties; however, no benefits have been reported to …

Е-постеры.

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Targeting cancer stem cells with CAR-based immunotherapy: biology, evidence, and future directions.

Cancer stem cells (CSCs) are pivotal in tumor initiation, progression, and relapse, underscoring the need for targeted therapies to achieve lasting responses. This review delves into CSC biology, highlighting their tumor-initiating potential demonstrated through limiting dilution assays and their role in resistance to therapies. Although successful CAR therapies, such as anti-CD19 CAR T-cells, can induce complete responses without directly targeting CSCs, CAR strategies focusing on CSCs may offer promising avenues to prevent recurrence. We assess CAR therapies targeting CSC-specific antigens,

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… PBMC-derived iNSCs expressing HSV-TK exhibited the tumor-tropism by migrating toward GBM cells. After reaching the tumors, they exerted anti-tumor activity, particularly in the presence of ganciclovir, which activates HSV-TK genes to eliminate tumor cells through the bystander effect. …

Emerging advances in drug delivery systems (DDSs) for optimizing cancer complications.

The management and treatment of tumor complications pose continuous challenges due to the inherent complexity. However, the advent of drug delivery systems (DDSs) brings promising opportunities to address the tumor complications using innovative technological approaches. This review focuses on common oncological complications, including cancer thrombosis, malignant serous effusion, tumor-associated infections, cancer pain, and treatment-related complications. Emphasis was placed on the application and potential of DDSs in mitigating and treating these tumor complications, and we delved into th

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… These vesicles have tissue tropism and can achieve targeted drug delivery through surface molecules such as integrins and glycans, showing great potential in drug delivery applications. …

Current State of Human Gene Therapy: Approved Products and Vectors.

In the realm of gene therapy, a pivotal moment arrived with Paul Berg's groundbreaking identification of the first recombinant DNA in 1972. This achievement set the stage for future breakthroughs. Conditions once considered undefeatable, like melanoma, pancreatic cancer, and a host of other ailments, are now being addressed at their root cause-the genetic level. Presently, the gene therapy landscape stands adorned with 22 approved in vivo and ex vivo products, including IMLYGIC, LUXTURNA, Zolgensma, Spinraza, Patisiran, and many more. In this comprehensive exploration, we delve into a rich ass

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… In addition, the strong tropism of HSV-1 for neurons makes it an ideal candidate for therapy of central nervous system diseases. However, the use of HSV-1 as a vector has some limitations. It may initiate a strong inflammatory response, which can be a concern for safety in some cases. …

Coronavirus Disease (COVID-19) Control between Drug Repurposing and Vaccination: A Comprehensive Overview.

Respiratory viruses represent a major public health concern, as they are highly mutated, resulting in new strains emerging with high pathogenicity. Currently, the world is suffering from the newly evolving severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus is the cause of coronavirus disease 2019 (COVID-19), a mild-to-severe respiratory tract infection with frequent ability to give rise to fatal pneumonia in humans. The overwhelming outbreak of SARS-CoV-2 continues to unfold all over the world, urging scientists to put an end to this global pandemic through biological and

Pharmacological treatments of COVID-19.

The viral infection due to the new coronavirus or coronavirus disease 2019 (COVID-19), which was reported for the first time in December 2019, was named by the World Health Organization (WHO) as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV2), because of the very similar genome and also its related symptoms to SARS-CoV1. The ongoing COVID-19 pandemic with significant mortality, morbidity, and socioeconomic impact is considered by the WHO as a global public health emergency. Since there is no specific treatment available for SARS-CoV2 infection, and or COVID-19, several clinical and

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… This drug has promising effects for an alteration of the viral tropism and the dynamics of human-to-human transmission when tested in a laboratory or clinical setting [ 108 ]. Clinical studies on the treatment of SARS-CoV2 by DRV are summarized in Table 2. …

Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy.

The advent of iPSCs has brought about a significant transformation in stem cell research, opening up promising avenues for advancing cancer treatment. The formation of cancer is a multifaceted process influenced by genetic, epigenetic, and environmental factors. iPSCs offer a distinctive platform for investigating the origin of cancer, paving the way for novel approaches to cancer treatment, drug testing, and tailored medical interventions. This review article will provide an overview of the science behind iPSCs, the current limitations and challenges in iPSC-based cancer therapy, the ethical

Drug repurposing for disease-modifying effects in multiple system atrophy.

Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder lacking any proven disease-modifying therapy. Drug repurposing offers a strategy to accelerate the development of treatments by utilizing agents originally approved for other indications. This review summarizes repurposed drugs investigated as disease-modifying therapies for MSA, spanning preclinical in vitro and animal studies and clinical trials. We focus on agents targeting key pathogenic mechanisms in MSA-including α-synuclein aggregation (e.g., sirolimus/rapamycin, rifampicin, lithium, nilotinib, epigallocat

Amino acids metabolism: a potential target for cancer treatment.

Metabolic reprogramming of amino acids has been recognized as a significant characteristic in various types of cancers. Numerous studies have indicated that the metabolic reprogramming of amino acids in tumors significantly supports certain malignant behaviors, including tumor proliferation, survival, invasion, and even immune escape. Amino acids can provide biomolecules such as nucleotides and glutathione (GSH) for tumors, and the bioavailability of amino acids influences tumor progression. Meanwhile, as essential metabolites, amino acids are closely associated with immune cell activation and

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… Zhou et al. developed MOF NPs αMM@PLTs to deliver α-methyl-DL-tryptophan (α-MT, a transporter SLC6A14 blockade drug), favoring US/GSH-responsive combinational therapeutics between glutamine deprivation and SDT [ 280 ]. αMM@PLT targets tumor sites through the inherent TME tropism of platelet (PLT) cells …

Translational Advances in Oncogene and Tumor-Suppressor Gene Research.

Cancer, characterized by the uncontrolled proliferation of cells, is one of the leading causes of death globally, with approximately one in five people developing the disease in their lifetime. While many driver genes were identified decades ago, and most cancers can be classified based on morphology and progression, there is still a significant gap in knowledge about genetic aberrations and nuclear DNA damage. The study of two critical groups of genes-tumor suppressors, which inhibit proliferation and promote apoptosis, and oncogenes, which regulate proliferation and survival-can help to unde

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… Adenoviruses and herpes simplex viruses are the most promising OVs, as they are easy to manipulate, have a clear genetic structure, can easily achieve gene transfer and tumor antigen expression, have a broad spectrum of host cell tropism, and can be prepared in large quantities [ 368 , 369 , 370 ]. …

Harnessing live vectors for cancer vaccines: Advancing therapeutic immunotherapy.

Cancer vaccines represent a promising approach within immunotherapies. These vaccines are tailored to target tumor-specific antigens, thereby offering a precision approach to cancer treatment. The key principles in developing therapeutic cancer vaccines include identifying appropriate vaccine targets and selecting effective vaccine delivery platforms. These delivery platforms are diverse and have evolved to enhance the immune response. This review explores live cancer vaccines and the biological entities involved. Live cancer vaccines leverage the use of various biological entities to stimulat