CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors

Cellular and Molecular Immunology, Год журнала: 2024, Номер 21(10), С. 1089 - 1108

Опубликована: Авг. 12, 2024

Abstract In the past decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers, demonstrating remarkable efficacy in relapsed/refractory hematological malignancies both pediatric and adult patients. CAR-natural killer (CAR-NK) complements CAR-T by offering several distinct advantages. CAR-NK cells do not require HLA compatibility exhibit low safety concerns. Moreover, are conducive to “off-the-shelf” therapeutics, providing significant logistic advantages over cells. Both have shown consistent results malignancies. However, their against solid tumors remains limited due various obstacles including tumor trafficking infiltration, well an immuno-suppressive microenvironment. this review, we discuss recent advances current challenges of immunotherapies, with specific focus on application tumors. We also analyze depth drawbacks compared highlight CAR optimization. Finally, explore future perspectives these adoptive highlighting increasing contribution cutting-edge biotechnological tools shaping next generation cellular immunotherapy.

Язык: Английский

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Beyond the blood: expanding CAR T cell therapy to solid tumors

Nature Biotechnology, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 12, 2024

Язык: Английский

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Emerging role of immunogenic cell death in cancer immunotherapy: Advancing next-generation CAR-T cell immunotherapy by combination

Cancer Letters, Год журнала: 2024, Номер 598, С. 217079 - 217079

Опубликована: Июнь 25, 2024

Язык: Английский

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The epitranscriptional factor PCIF1 orchestrates CD8+ T cell ferroptosis and activation to control antitumor immunity

Nature Immunology, Год журнала: 2025, Номер 26(2), С. 252 - 264

Опубликована: Янв. 6, 2025

Язык: Английский

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Targeting the gut microbiota to enhance the antitumor efficacy and attenuate the toxicity of CAR-T cell therapy: a new hope?

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Март 15, 2024

Chimeric antigen receptor (CAR) -T cell therapy has achieved tremendous efficacy in the treatment of hematologic malignancies and represents a promising regimen for cancer. Despite striking response patients with malignancies, most solid tumors treated CAR-T cells have low rate experience major adverse effects, which indicates need biomarkers that can predict improve clinical outcomes future treatments. Recently, role gut microbiota cancer been established, growing evidence suggested signatures may be harnessed to personally therapeutic or effects optimizing therapy. In this review, we discuss current understanding microbiota, interplay between Above all, highlight potential strategies challenges harnessing as predictor modifier while attenuating toxicity.

Язык: Английский

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Basic Concepts and Indications of CAR T Cells

Hämostaseologie, Год журнала: 2025, Номер 45(01), С. 014 - 023

Опубликована: Фев. 1, 2025

Abstract Chimeric antigen receptor (CAR) T cell therapy has revolutionized cancer immunotherapy, particularly for hematological malignancies. This personalized approach is based on genetically engineering cells derived from the patient to target antigens expressed—among others—on malignant cells. Nowadays they offer new hope where conventional therapies, such as chemotherapy and radiation, have often failed. Since first FDA approval in 2017, CAR rapidly expanded, proving highly effective against previously refractory diseases with otherwise a dismal outcome. Despite its promise, continues face significant challenges, including complex manufacturing, management of toxicities, resistance mechanisms that impact long-term efficacy, limited access well high costs, which continue shape ongoing research clinical applications. review aims provide an overview therapy, fundamental concepts, applications, current future directions

Язык: Английский

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A chimeric antigen receptor tailored to integrate complementary activation signals potentiates the antitumor activity of NK cells

Journal of Experimental & Clinical Cancer Research, Год журнала: 2025, Номер 44(1)

Опубликована: Март 6, 2025

Chimeric antigen receptors (CARs) are synthetic that reprogram the target specificity and functions of CAR-expressing effector cells. The design CAR constructs typically includes an extracellular antigen-binding moiety, hinge (H), transmembrane (TM), intracellular signaling domains. Conventional primarily designed for T cells but have been directly adopted other cells, including natural killer (NK) without tailored optimization. Given benefits CAR-NK over CAR-T in terms safety, off-the-shelf utility, escape, there is increasing emphasis on tailoring them to NK cell activation mechanisms. We first taken a stepwise approach modifying components such as combination order H, TM, domains achieve Functionality NK-tailored CARs were evaluated vitro vivo model CD19-expressing lymphoma, along with their expression properties found NK-CAR driven by synergistic NKG2D 2B4 rather than DNAM-1 induces potent Further, more effective CAR-mediated cytotoxicity was observed following sequential DAP10, not domain despite capacity TM recruit endogenous DAP10 signaling. Accordingly, incorporating 2B4, CD3ζ coupled CD8α H CD28 identified most promising candidate improve cytotoxicity. This provided antitumor activity conventional T-CAR when delivered both vivo. Hence, receptor-based hold great promise future potentially significant therapeutic benefits.

Язык: Английский

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Optimizing CAR-T cell therapy for solid tumors: current challenges and potential strategies

Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)

Опубликована: Ноя. 5, 2024

Chimeric antigen receptor (CAR)-T cell therapy demonstrates substantial efficacy in various hematological malignancies. However, its application solid tumors is still limited. Clinical studies report suboptimal outcomes such as reduced cytotoxicity of CAR-T cells and tumor evasion, underscoring the need to address challenges sliding cells. Despite improvements from fourth next-generation cells, new include systemic toxicity continuously secreted proteins, low productivity, elevated costs. Recent research targets genetic modifications boost killing potential, metabolic interventions hinder progression, diverse combination strategies enhance therapy. Efforts reduce duration cost developing allogenic in-vivo approaches, promising significant future advancements. Concurrently, innovative technologies platforms potential overcome limitations treating tumors. This review explores optimize therapies for tumors, focusing on enhancing overcoming restrictions. We summarize recent advances T subset selection, structural modifications, infiltration enhancement, interventions, production optimization, integration novel technologies, presenting therapeutic approaches that could improve therapy's applicability

Язык: Английский

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CAR-T cell therapy for hepatocellular carcinoma: current trends and challenges

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Ноя. 6, 2024

Hepatocellular carcinoma (HCC) ranks among the most prevalent cancers worldwide, highlighting urgent need for improved diagnostic and therapeutic methodologies. The standard treatment regimen generally involves surgical intervention followed by systemic therapies; however, median survival rates patients remain unsatisfactory. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a pivotal advancement in cancer treatment. Both clinical preclinical studies emphasize notable efficacy of CAR T cells targeting HCC. Various molecules, such GPC3, c-Met, NKG2D, show significant promise potential immunotherapeutic targets liver cancer. Despite this, employing to treat solid tumors like HCC poses considerable challenges within discipline. Numerous innovations have enhance HCC, including improvements cell trafficking, strategies counteract immunosuppressive tumor microenvironment, enhanced safety protocols. Ongoing efforts discover highlight development more practical manufacturing CAR-modified cells. This review synthesizes recent findings advancements use therapies We elucidate benefits identify primary barriers their broader application. Our analysis aims provide comprehensive overview current status future prospects immunotherapy

Язык: Английский

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Application of novel CAR technologies to improve treatment of autoimmune disease

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Окт. 9, 2024

Chimeric antigen receptor (CAR) T cell therapy has become an important treatment for hematological cancers, and its success spurred research into CAR therapies other diseases, including solid tumor cancers autoimmune diseases. Notably, the development of CAR-based treatments diseases shown great progress recently. Clinical trials anti-CD19 anti-BCMA cells in treating severe B cell-mediated like systemic lupus erythematosus (SLE), have lasting remission thus far. targeting autoreactive are beginning clinical mediated autoantigen (CAAR) specifically target eliminate only cells, they promise mucosal pemphigus vulgaris MuSK myasthenia gravis. Regulatory also been developed, which show potential altering affected areas by creating a protective barrier as well helping decrease inflammation. These new applications disease. Novel technologies developed that increase safety, potency, specificity, efficacy therapy. Applying these novel modifications to CARs enhance applicability This review will detail several recently discuss how their application disease improve this emerging field. include logic-gated CARs, soluble protein-secreting modular enable be more specific, reach wider span safer patients, give potent cytotoxic response. revolutionize growing therapies.

Язык: Английский

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