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Evolving strategies for addressing CAR T-cell toxicities.

The field of chimeric antigen receptor (CAR) T-cell therapy has grown from a fully experimental concept to now boasting a multitude of treatments including six FDA-approved products targeting various hematologic malignancies. Yet, along with their efficacy, these therapies come with side effects requiring timely and thoughtful interventions. In this review, we discuss the most common toxicities associated with CAR T-cells to date, highlighting risk factors, prognostication, implications for critical care management, patient experience optimization, and ongoing work in the field of toxicity mit

34th Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2019): part 2 : National Harbor, MD, USA. 10 November 2019.

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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

Совпадение в полном тексте источника
… Furthermore, exhausted CD8 + T cells exhibit decreased levels of perforin and granzymes, which are essential for the effective elimination of infected or malignant cells. 2 Notably, even at most terminal stages, exhausted CD8 + T cells retain some cytotoxic activity and secrete granzyme B, thereby maintaining …

Metabolic reprogramming and therapeutic resistance in primary and metastatic breast cancer.

Metabolic alterations, a hallmark of cancer, enable tumor cells to adapt to their environment by modulating glucose, lipid, and amino acid metabolism, which fuels rapid growth and contributes to treatment resistance. In primary breast cancer, metabolic shifts such as the Warburg effect and enhanced lipid synthesis are closely linked to chemotherapy failure. Similarly, metastatic lesions often display distinct metabolic profiles that not only sustain tumor growth but also confer resistance to targeted therapies and immunotherapies. The review emphasizes two major aspects: the mechanisms driving

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… Cytotoxic T lymphocytes (CTLs) CTLs are the primary components of anti-tumor cellular immunity, directly killing tumor target cells by secreting perforin and granzyme or by expressing apoptosis-related factor ligands and secreting TNF-α, which bind to receptors on the target cell surface, inducing apoptosis …

Immunotherapy in hematologic malignancies: achievements, challenges and future prospects.

The immune-cell origin of hematologic malignancies provides a unique avenue for the understanding of both the mechanisms of immune responsiveness and immune escape, which has accelerated the progress of immunotherapy. Several categories of immunotherapies have been developed and are being further evaluated in clinical trials for the treatment of blood cancers, including stem cell transplantation, immune checkpoint inhibitors, antigen-targeted antibodies, antibody-drug conjugates, tumor vaccines, and adoptive cell therapies. These immunotherapies have shown the potential to induce long-term rem

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… In this way, the modified T cells can be activated in an MHC-independent manner by directly binding with specific tumor antigens and directly killing the tumor cells by releasing perforin, granzyme B, etc. and also by secreting cytokines to recruit human endogenous immune cells to help to kill tumor …

Резюме

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Targeting cytokine and chemokine signaling pathways for cancer therapy.

Cytokines are critical in regulating immune responses and cellular behavior, playing dual roles in both normal physiology and the pathology of diseases such as cancer. These molecules, including interleukins, interferons, tumor necrosis factors, chemokines, and growth factors like TGF-β, VEGF, and EGF, can promote or inhibit tumor growth, influence the tumor microenvironment, and impact the efficacy of cancer treatments. Recent advances in targeting these pathways have shown promising therapeutic potential, offering new strategies to modulate the immune system, inhibit tumor progression, and o

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… aiding pathogen clearance, while also preventing excessive immune activation and tissue damage. 88 In the TME, IFN-γ exhibits both protumor and antitumor activities, which are largely dependent on the duration and magnitude of the signaling. 89 Initially identified as a cytotoxic cytokine, along with perforin …

Abstract

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CAR-T cell therapy for cancer: current challenges and future directions.

Chimeric antigen receptor T (CAR-T) cell therapies have transformed the treatment of relapsed/refractory (R/R) B-cell malignancies and multiple myeloma by redirecting activated T cells to CD19- or BCMA-expressing tumor cells. However, this approach has yet to be approved for acute myeloid leukemia (AML), the most common acute leukemia in adults and the elderly. Simultaneously, CAR-T cell therapies continue to face significant challenges in the treatment of solid tumors. The primary challenge in developing CAR-T cell therapies for AML is the absence of an ideal target antigen that is both effec

Резюме ЭСП 2013.

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Cancer stem cells: advances in knowledge and implications for cancer therapy.

Cancer stem cells (CSCs), a small subset of cells in tumors that are characterized by self-renewal and continuous proliferation, lead to tumorigenesis, metastasis, and maintain tumor heterogeneity. Cancer continues to be a significant global disease burden. In the past, surgery, radiotherapy, and chemotherapy were the main cancer treatments. The technology of cancer treatments continues to develop and advance, and the emergence of targeted therapy, and immunotherapy provides more options for patients to a certain extent. However, the limitations of efficacy and treatment resistance are still i

The 48th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians - Oral Sessions (O009-O155).

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Резюме книги: ISEV2017.

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33rd Европейский конгресс патологии - резюме.

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… Immunohistochemical determination of the surface markers of CD3, CD20, CD45, CD 68, perforin, TLR-4, TLR-9 and SARS-CoV-2 nucleocapsid and spike-protein were presented. …

ИАНКОН 2023 Выдержки из плаката

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ISEV2018 абстрактная книга

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Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges. A critical process induced by TME signaling is the epithelial-mesenchymal transition (EMT), wherein epithelial cells acquire mesenchymal traits, which enhance their motility and inva

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… Upon identifying a target, NK cells release cytotoxic granules containing perforin and granzymes, which induce apoptosis in the target cells. …

Р

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The 48th Annual Meeting of the European Society for Blood and Marrow Transplantation: Physicians - Poster Session (P001 - P578).

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Program-Abstracts

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