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T Cell Based Immunotherapy for Cancer: Approaches and Strategies.

T cells are critical in destroying cancer cells by recognizing antigens presented by MHC molecules on cancer cells or antigen-presenting cells. Identifying and targeting cancer-specific or overexpressed self-antigens is essential for redirecting T cells against tumors, leading to tumor regression. This is achieved through the identification of mutated or overexpressed self-proteins in cancer cells, which guide the recognition of cancer cells by T-cell receptors. There are two main approaches to T cell-based immunotherapy: HLA-restricted and HLA-non-restricted Immunotherapy. Significant progres

An expanding horizon of complex injectable products: development and regulatory considerations.

There has been a constant evolution in the pharmaceutical market concerning the new technologies imbibed in delivering drug substances for various indications. This is either market-driven or technology-driven to improve the overall therapeutic efficacy and patients' quality of life. The pharmaceutical industry has experienced rapid growth in the area of complex injectable products because of their effectiveness in the unmet market. These novel parenteral products, viz, the nanoparticles, liposomes, microspheres, suspensions, and emulsions, have proven their worth as "Safe and Effective" produ

Regulatory role of PI3K/Akt/WNK1 signal pathway in mouse model of bone cancer pain.

In the advanced stage of cancer, the pain caused by bone metastasis is unbearable, but the mechanism of bone cancer pain (BCP) is very complicated and remains unclear. In this study, we used 4T1 mouse breast cancer cells to establish a bone cancer pain model to study the mechanism of BCP. Then the paw withdrawal mechanical threshold (PWMT) and the hematoxylin-eosin staining were used to reflect the erosion of cancer cells on tibia tissue. We also determined the role of proinflammatory factors (TNF-α, IL-17, etc.) in BCP by the enzyme-linked immunosorbent assay in mouse serum. When GSK690693, a

Recognition and management of early complications in CAR-T cell therapy and virus-specific T-lymphocyte therapy: a practical clinical reference.

BACKGROUND: Cellular immunotherapies-including chimeric antigen receptor T-cell (CAR-T) therapies and adoptive transfer of virus-specific T lymphocytes (VSTs) - have transformed the treatment of refractory hematological malignancies and post-transplant infectious complications. Eight products are currently authorized by the European Medicines Agency, encompassing seven autologous CAR-T products targeting CD19 or BCMA and tabelecleucel (Ebvallo), the first approved allogeneic off-the-shelf EBV-specific T-cell product for EBV-positive post-transplant lymphoproliferative disease. Despite their cl

2020 CIS Annual Meeting: Immune Deficiency & Dysregulation North American Conference.

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Castleman Disease and Kaposi Sarcoma: A Review of the Literature and a Case Series.

Castleman disease and Kaposi sarcoma (KS) are both associated with infection by human herpesvirus 8 (HHV-8), also known as Kaposi's sarcoma-associated herpesvirus (KSHV). This virus plays a critical role in the pathogenesis of both conditions, particularly in immunocompromised individuals, such as those with HIV/AIDS. Multicentric Castleman disease (MCD) generally presents with systemic inflammatory symptoms, lymphadenopathy, and organ dysfunction, while Kaposi sarcoma typically appears as vascular tumors on the skin, with occasional involvement of mucous membranes or internal organs. We prese

Long-Term Effects of Pediatric Acute Lymphoblastic Leukemia Chemotherapy: Can Recent Findings Inform Old Strategies?

During the last few decades, pediatric acute lymphoblastic leukemia (ALL) cure rates have improved significantly with rates exceeding 90%. Parallel to this remarkable improvement, there has been mounting interest in the long-term health of the survivors. Consequently, modified treatment protocols have been developed and resulted in the reduction of many adverse long-term consequences. Nevertheless, these are still substantial concerns that warrant further mitigation efforts. In the current review, pediatric-ALL survivors' late adverse events, including secondary malignant neoplasms (SMNs), car

" Окно " в новых представлениях о прогрессе, независимом от активности релапса в многоразовом склерозе: роль терапии и текущие перспективы.

В случае множественного склероза (МС) имеются значительные данные, указывающие на то, что как прогресс, не зависящий от активности рецидивов (ИПРА), так и ухудшение ситуации, связанное с рецидивами, способствуют накоплению постепенной инвалидности с самого начала заболевания и на протяжении всего его периода. Понимание разрозненной патофизиологии MS способствовало бы более глубокому пониманию механизмов развития заболеваний и преодолению традиционного различия в фенотипах. Похоже, что деятельность по сморщению MS поддерживается постоянным взаимодействием между паренхимными хроническими процесс

Воздействие витамина D на герпесвирусные инфекции.

Помимо своей классической роли в регулировании метаболизма кальция и фосфата, витамин D также оказывает значительное влияние на модуляцию иммунитета. Витамин D регулирует иммунную реакцию, переходя от воспламенительного состояния к более толерогенному one путем увеличения выброса антивоспалительных цитокинов при одновременном ослаблении регулирования проинфламаторных цитокинов. Таким образом, низкий уровень витамина D связан с повышенным риском возникновения аутоиммунных заболеваний, таких, как множественный склероз и тип 1 диабет. Кроме того, этот прохормон также способствует высвобождению хо

Anti-cancer effects of nitrogen-containing bisphosphonates on human cancer cells.

Zoledronic acid, a potent nitrogen-containing bisphosphonate (NBP), has been extensively used to limit bone turnover in a various diseases including tumors. Recent clinical studies have demonstrated direct anti-cancer effects of zoledronic acid, in addition to its clinical benefits for skeletal-related events. Here we investigated the effects of 4 clinically available NBPs on human tumor cell proliferation. Our data demonstrate a potent anti-proliferative effect of zoledronic acid against glioblastoma (GBM) cell lines, breast cancer cells and GBM patient-derived lines. Zoledronic acid also eff

Role of Bruton's tyrosine kinase in B cells and malignancies.

Bruton's tyrosine kinase (BTK) is a non-receptor kinase that plays a crucial role in oncogenic signaling that is critical for proliferation and survival of leukemic cells in many B cell malignancies. BTK was initially shown to be defective in the primary immunodeficiency X-linked agammaglobulinemia (XLA) and is essential both for B cell development and function of mature B cells. Shortly after its discovery, BTK was placed in the signal transduction pathway downstream of the B cell antigen receptor (BCR). More recently, small-molecule inhibitors of this kinase have shown excellent anti-tumor a

Мак-1 регулирует иммуноусилительное подавление конкретной стадии болезни через нитриковый путь в аутоиммунном заболевании.

Интегрин Мак-1 играет важнейшую роль в развитии множественного склероза (MS); однако лежащий в его основе механизм не в полной мере изучен. Здесь мы разработали мышь с миелоидной мышью Мак-1-дефицит. Используя экспериментальную аутоиммунную энцефаломиэлит (EAE) модель мыши MS, мы сообщаем, что Мак-1 на миелиоидных клетках является ключом к развитию болезней. Наши данные показывают, что миелиоидный Мак-1 значительно повышает интенсивность EAE и затрудняет регрессию заболеваний. Потеря Mac-1 увеличивает количество клеток Gr-1+ в периферийных тканях и CNS и предпочтительно ускоряет переход моноци

Свойства антиракера ВИЧ-ингибатора Нелфинавира.

Традиционные методы лечения рака могут потерять свою эффективность после появления новых мутации или развития химиотерапии. Несвоевременная диагностика, высокая стоимость лечения и потребность в высокоэффективной инфраструктуре для лечения раковых заболеваний затрудняют доступ к надлежащему лечению в условиях с низким уровнем доходов и ограниченными ресурсами. Переориентация утвержденных лекарственных средств на лечение рака может привести к снижению стоимости и сокращению сроков разработки новых лекарственных средств и к ускорению появления новых и эффективных вариантов лечения для нуждающихс

Regulatory T cells and immune escape in HCC: understanding the tumor microenvironment and advancing CAR-T cell therapy.

Liver cancer, which most commonly manifests as hepatocellular carcinoma (HCC), is the sixth most common cancer in the world. In HCC, the immune system plays a crucial role in the growth and proliferation of tumor cells. HCC achieve immune escape through the tumor microenvironment, which significantly promotes the development of this cancer. Here, this article introduces and summarizes the functions and effects of regulatory T cells (Tregs) in the tumor microenvironment, highlighting how Tregs inhibit and regulate the functions of immune and tumor cells, cytokines, ligands and receptors, etc, t

Plumbagin, a Biomolecule with (Anti)Osteoclastic Properties.

Plumbagin is a plant-derived naphthoquinone that is widely used in traditional Asian medicine due to its anti-inflammatory and anti-microbial properties. Additionally, plumbagin is cytotoxic for cancer cells due to its ability to trigger reactive oxygen species (ROS) formation and subsequent apoptosis. Since it was reported that plumbagin may inhibit the differentiation of bone resorbing osteoclasts in cancer-related models, we wanted to elucidate whether plumbagin interferes with cytokine-induced osteoclastogenesis. Using C57BL/6 mice, we unexpectedly found that plumbagin treatment enhanced o

HIV-Associated Lymphomas: Updates from Pathogenesis to Treatment Strategies.

HIV-associated lymphoma (HAL) is an aggressive malignancy directly linked to HIV infection and accounts for more than 30% of cancer-related deaths in people living with HIV (PLWH). HAL subtypes, including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), primary effusion lymphoma (PEL), and plasmablastic lymphoma (PBL), exhibit five to ten times higher incidence rates and distinct molecular profiles compared to HIV-negative lymphomas. Pathogenesis involves HIV-driven CD4+ T-cell depletion, chronic B-cell activation, and oncogenic viral coinfection. First-line therapy combines antir

Targeting the FGFR signaling pathway in cholangiocarcinoma: promise or delusion?

Cholangiocarcinoma (CCA) is a refractory cancer with limited treatment options and poorly understood molecular mechanisms underlying tumor development. The most effective treatment is surgical resection; however, patients are highly prone to recurrence. Moreover, considering that most patients are diagnosed in advanced stages, treatment options are restricted to palliative care, which results in poor prognosis. Due to the limited effect of chemotherapy and radiotherapy, targeted therapy is becoming a hot topic in the field of biliary cancer treatment. The fibroblast growth factor/fibroblast gr

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… By analyzing pretreatment and post-progression cell-free circulating tumor DNA (cfDNA) in three advanced CCA patients after BGJ398 treatment, Goyal et al. found that FGFR2 point mutations (p.N549H, p.N549K, p.V564F, p.E565A, and p.K659M, p.N549H, p.E565A, p.L617V, and p.K641R) could lead to clinical …

Update on preclinical models of cancer therapy-related cardiac dysfunction: Challenges and perspectives. A scientific statement of the Heart Failure Association (HFA) of the ESC, the ESC Council of Cardio-Oncology, and the ESC Working Group on Cellular Biology of the Heart.

New anticancer therapies with potential cardiovascular side effects are continuously being introduced into clinical practice, with new and often unexpected toxicities becoming apparent only after clinical introduction. These unknown toxicities should be identified and understood beforehand to better prepare patients and physicians, enabling the implementation of effective treatments. Therefore, there is a crucial need for appropriate preclinical models to understand the biological basis of their cardiotoxicity. This scientific statement summarizes the preclinical models hitherto used, from in

Lung cancer immunotherapy: progress, pitfalls, and promises.

Lung cancer is the primary cause of mortality in the United States and around the globe. Therapeutic options for lung cancer treatment include surgery, radiation therapy, chemotherapy, and targeted drug therapy. Medical management is often associated with the development of treatment resistance leading to relapse. Immunotherapy is profoundly altering the approach to cancer treatment owing to its tolerable safety profile, sustained therapeutic response due to immunological memory generation, and effectiveness across a broad patient population. Different tumor-specific vaccination strategies are

Overcoming temozolomide resistance in glioma: recent advances and mechanistic insights.

Temozolomide (TMZ) remains the cornerstone chemotherapy for glioma, yet intrinsic and acquired resistance mechanisms significantly limit its clinical effectiveness. This review summarizes the multifaceted molecular pathways contributing to TMZ resistance, including enhanced DNA repair mechanisms such as O6-methylguanine-DNA methyltransferase (MGMT), mismatch repair (MMR), and base excision repair (BER). Additional resistance factors include genetic mutations that affect the drug response, dysregulated non-coding RNAs (miRNAs, lncRNAs, and circRNAs), glioma stem cells (GSCs), cytoprotective aut