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Cd19 car t cell therapy review A total of 12 studies provide data on the outcomes of patients with a minimum median follow-up duration of 1 year (range 1–4. This review aims to provide a comprehensive CAR therapy has the potential to offer a rapid and safer treatment regime to treat non‑solid and solid tumors. at our center reported that, among patients who did not undergo subsequent allogeneic Background: This study aimed to systematically evaluate and compare the efficacy and safety of consolidative hematopoietic stem cell transplantation (HSCT) after CD19 chimeric antigen receptor T (CAR-T) therapy with non-HSCT in the treatment of acute lymphoblastic leukemia (ALL). Importantly longer leukemia-free survival of animals was observed when using a 4-1 BB second-generation CAR consistent with longer persistence of 4-1BB-stimulated CART. Indeed, many of these cases, when centrally reviewed, are reclassified as DLBCL or BL. Currently, CD19 CAR T cells induced a rapid and sustained depletion of circulating B cells, as well as in a complete clinical and serological remission of refractory systemic lupus reviews on CAR T-cell therapy into our references. Previously, the high frequency of severe adverse events was a major concern. Methods: We collected data from Embase, Web of Science, PubMed, CNKI, Wanfang and Cochrane databases up to April 2023. However, the complete risk profile of CAR T-cells could not be defined in the initial trials. In this Review, we provide guidance for a rational management approach to A total of 10 to 20 billion cells are required for mRNA CAR-T therapy, compared with 100 to 500 million cells for approved conventional CAR-T therapies. Conventional chemotherapies show poor efficacy in B-ALL patients who have relapsed following allo-HSCT. Comparison studies are required to further determine differences Despite the safety and high remission rate of CD19 CAR-T cell therapy in B-ALL, approximately 30-50% of patients experience a second recurrence within 3–12 months after CD19 CAR-T therapy [3, 4]. Anti-CD19 CAR T-cells currently represent transformational therapy for relapsed/refractory aggressive B-cell lymphomas where durable remissions can be Early results from CAR T cell trials evaluating other targets indicated that the CD19 off-tumor cross-reactions are not a singular example, but may be generally observed This review summarizes evidence regarding cellular immunotherapies for cancer. This includes dual targeting of CD19 and CD22 CAR T cell treatments. The first product, Axicabtagen (Axi-cel) is a CD19 CAR T-cell with CD28 as a co-stimulatory molecule. Data are now available from multiple long-term follow-up studies of the efficacy of CD19-targeted CAR T cell therapy in patients with B-ALL 18,42–53. By selectively depleting CD19-positive B-cells, this therapy brings a new approach in resetting immune dysregulation and potentially providing long-term The CAR-HEMATOTOX score was developed in the setting of anti-CD19 CAR-T cell therapy for B-cell malignancies, and has recently been validated in MM. Methods: The PubMed, Embase, Cochrane Library and Web of Science After undergoing lymphodepleting conditioning, wherein patients are subjected to a form of chemotherapy targeting their immune cells (typically using fludarabine and cyclophosphamide), approximately 10 8 viable CAR-T cells are administered into patients through an intravenous infusion at an authorized healthcare facility. Dose fractionation of CAR CD19-CAR T-cell therapy with sorafenib in post-HSCT relapse of mixed phenotype acute leukaemia (MPAL) with phenotypic myeloid to lymphoid lineage switch-A case report and review of the literature Br J Haematol . After With the focus on prolonged cytopenia in this review, we aim to summarize findings of various clinical trials, postulated mechanisms, and clinical interventions to risk-stratify and manage this clinical entity. The effects of CD19-targeting CAR T cells on organ manifestations in patients with systemic sclerosis have yet to be characterised. Dr. In Australia, the Over the past few years, dual-targeted chimeric antigen receptor (CAR) T-cell therapy has been employed in the management of hematological malignancies to mitigate treatment failure, particularly in cases of antigen escape. It is believed that the combination of CAR-T cell therapy with P: participants (RRMM patients), I: interventions (combined anti-BCMA and anti-CD19 CAR-T cell therapy), C: comparisons (this analysis included single-arm studies without a control group), O: outcomes (the outcome was the efficacy and safety of combined anti-BCMA and anti-CD19 CAR-T cell therapy), S: study designs (Phase I and II clinical In the last 2 years treatment with autologous CAR T cells directed against the CD19 antigen has been introduced in therapy of autoimmune disease. Results: The pooled complete remission (CR) rate Background Chimeric antigen receptor CAR-T cell therapies have ushered in a new era of treatment for specific blood cancers, offering unparalleled efficacy in cases of treatment resistance or relapse. . In a CAR T cells are now an established treatment for patients with relapsed and/or refractory B cell lymphomas, B cell acute lymphoblastic leukaemia and multiple myeloma. Nine studies reported the assessment of treatment complete responses. CAR T-cell therapy targeting CD19 has proven highly effective in patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL), and several p. Designed to seek out and engage CD19-expressing B lymphocytes, the current anti-CD19 CAR T-cell therapies indiscriminately attack healthy and malignant B lymphocytes. Ther Here we provide a thorough review on the use of the FDA approved anti-CD19 CAR T-cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel in patients with indolent or aggressive B-cell lymphoma, and touch on mechanisms of failure of CAR T-cell therapy and potential approaches which are currently under investigation Background: CD22 single and CD19/CD22 bispecific targeted chimeric antigen receptor T (CAR-T) cell therapy are promising immunotherapy modalities for the treatment of hematologic malignancies. In addition, although the ability to re-treat patients could ultimately be beneficial, the treatment regimens in the trial above involved multiple outpatient infusions, which add an additional Pharmacology of CAR T-Cell Therapies. Although allo-HSCT can be curative for some B-ALL patients, relapse still occurs in some patients following allo-HSCT. CAR T-cell products are approved for the treatment of B-cell CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive results in treating acute lymphoblastic leukemia (B-ALL), chronic lymphoblastic leukemia (B-CLL), and B-cell non-Hodgkin lymphoma (B-NHL) over the past few years. 4 Another trial, NCT02706405, indicated that initiating anti-PD-L1 antibody CD19-directed autologous chimeric antigen receptor (auto-CAR) T cells have been transformative in the treatment of patients with r/r B cell malignancies. 18 It is quite encouraging that profound and durable B-cell depletion was achieved by the anti-CD19 CAR-T cell regimen not only as After undergoing lymphodepleting conditioning, wherein patients are subjected to a form of chemotherapy targeting their immune cells (typically using fludarabine and cyclophosphamide), approximately 10 8 viable CAR-T cells are administered into patients through an intravenous infusion at an authorized healthcare facility. Chimeric antigen receptor (CAR)-T cell therapy has been confirmed improving remission rates in refractory patients or relapsed B-cell acute lymphoblastic leukemia (R/R B-ALL). of resistance can inform on the design of novel treatment approaches for patients predicted to respond poorly to SOC CAR-T. Anti-CD19 CAR-T-cell cannot kill B-cells with hemizygous deletions spanning Incomplete clearance of BCP-ALL by blinatumomab may also predict resistance to CD19-CAR-T cell therapy [2,207]. BMC Cancer. 3,4 The success of CD19 CAR T-cell therapy is based on the deep B-cell depletion they can induce. In patients 25 years of age or younger CART19 therapy is an accepted standard of Chimeric Ag receptor (CAR) T cell therapy is a cancer treatment that genetically alters a patient’s own T cells to recognize the CD19 Ag or other Ags present on B cell and other malignancies (). Articles related to autologous and allogenic stem cell transplantation in autoimmune diseases, as well as studies related to Review Article. Anti-CD19 chimeric antigen receptor (CAR) T cell therapies can cause severe cytokine-release syndrome (CRS) and neurotoxicity, impeding their therapeutic application. Volkov, Nunez, and colleagues show CABA-201, a human anti-CD19 41BBζ CAR T cell product, rapidly and transiently eliminates B cells in an immune-mediated necrotizing myopathy subject, leading to decreases in serum CK and auto-antibodies and improvements in muscle strength. Chimeric antigen receptor (CAR) T-cell therapy represents a major advancement in personalized cancer treatment. CD19 chimeric antigen receptor–modified T cell (CAR-T) therapy has shown promising results in RR–B-ALL. In 2017, CAR T cell therapy became an Food and The CD19-directed chimeric antigen receptor (CAR) T-cell therapies axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel) have been approved over the past 15 months for the second-line treatment of patients with high-risk large B-cell lymphoma (LBCL), and have had a substantial effect on current algorithms for the salvage treatment of the disease. Understanding the limitations of CAR T cell therapy will be critical to realizing the full potential of this novel treatment approach. Results: Different anti-CD19 CAR T-cell therapy Abstract CD19-directed autologous chimeric antigen receptor T cell (CAR-T) therapy has transformed the management of relapsed/refractory (R/R) large B cell lymphoma (LBCL). 87, the pooled estimate of CR rate of CD19/CD22 bispecific CAR-T cell therapy was higher than that of CD19 targeted CAR-T cell therapy as reported in Meng et al. This procedure, supported by data Chimeric antigen receptor (CAR)-T cell therapy has been confirmed improving remission rates in refractory patients or relapsed B-cell acute lymphoblastic leukemia (R/R B-ALL). B cells have a central role in the pathogenesis of systemic sclerosis. This procedure, supported by data This review discusses the potential of CD19 CAR-T cells in ARDs, highlighting clinical achievements and addressing key considerations such as optimal target cell populations, CAR construct design, acceptable toxicities, and the potential for lasting immune reset, crucial for the safe and effective adoption of CAR-T cell therapy in autoimmune Aims: To review recent data and relevant of the role of anti-CD19 chimeric antigen receptor (CAR) T-cell therapy for B-cell non-Hodgkin lymphoma (NHL). In this Chimeric antigen receptor T cell therapy targeting CD19 (CART19) has shown remarkable results in patients with relapsed/refractory (r/r) B cell acute lymphoblastic leukemia (ALL). 1 Pharmacology of CAR T-Cell Therapies. In this review, we have provided an overview of currently approved CAR‐T therapies and upcoming clinical trials which may potentially impact the clinical practice. With its relative safety and efficacy, the Food and Drug Administration (FDA) Anti-CD19 CAR-T cell therapy bridge to HSCT decreases the relapse rate and improves the long-term survival of R/R B-ALL patients: a systematic review and meta-analysis Ann Hematol . Brexu‐cel is the first anti‐CD19 CAR‐T cell therapy approved for/R MCL. Here, we evaluated the influence of different hinge, transmembrane (TM), and costimula A total of 10 to 20 billion cells are required for mRNA CAR-T therapy, compared with 100 to 500 million cells for approved conventional CAR-T therapies. A. However, the added benefits of undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T therapy remain a subject of debate. However, the potential side effects of therapy, particularly cytokine release syndrome (CRS) and infections, pose significant challenges due Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective therapy for B-cell acute lymphoblastic leukemia (B-ALL). Singh and Maus review the fundamentals of function of these receptors; recent advances in gene, genome and protein editing that have propelled advanced engineering of CAR T cells; and look toward the next decade of progress in synthetic immunity. Food and Drug Administration. 1007/s00277-021-04451-w. Clinical studies report suboptimal outcomes such as reduced cytotoxicity of CAR-T cells and tumor evasion, underscoring the need to address the challenges of sliding cytotoxicity in CAR-T In August 2017, Novartis Kymriah (CAR-T cells targeting CD19) was approved by the FDA, indicating the real entry of CAR-T cell therapy into clinical applications and making CAR-T cell therapy the most attractive technology in the field of tumor treatment. However, there is a growing interest in the transition to outpatient administration due to multiple reasons. The histologic and biologic overlap of these high-grade entities, In this review we summarize key predictors of CAR T-cell efficacy in lymphomas and outline mechanisms of immune escape related to both solid tumors and lymphomas in order to identify the most promising trends for future development of CAR T-cell therapy. A genetically engineered, healthy donor-derived CD19-targeted chimeric antigen receptor (CAR)-T cell treatment achieved safe, deep remission in one patient with severe immune-mediated necrotizing myopathy and two patients with diffuse cutaneous systemic sclerosis, highlighting the potential of off-the-shelf CAR-T therapy in advancing clinical management of severe refractory Recently, an early phase 1 clinical trial has started to evaluate the effectiveness of CD19-BAFF CAR-T cell therapy for autoimmune diseases (NCT06279923). This study aimed to evaluate its efficacy and safety in treating relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL). Here we present an updated patient cohort of 30 patients with longer follow-up from a monocentric experience. Following the preclinical rationale that less-differentiated plasma cell subsets may only be targetable after debulking of CD19-negative MM cells, the first clinical trials in MM investigated CD19-directed CAR-T cell therapy as a consolidation strategy after autologous stem cell transplantation (ASCT, Table 1). The approval of several CD19-targeted CAR T-cell therapies has resulted in a notable surge in clinical trials involving CAR T cell therapies for hematological malignancies. This review aims to provide a comprehensive 2. CD19-targeted chimeric antigen receptor T cells (CAR T) therapy has shown prominent efficacy in relapsed/refractory (R/R) B cell malignancies with rapid response and long term remission (). 32% of all clinical trials target hematological cancers but not CD19. Recent studies suggest patients who underwent post-chimeric antigen receptor T cell therapy hematopoietic stem cell transplantation (post- HSCT) would achieve durable The high response rates after anti-CD19 CAR T-cell therapy can be used to guide the use of therapy in patients with relapsed or refractory acute lymphocytic leukaemia. The therapy at NCI involved the use of a retroviral vector called MSGV to express a CD19-specific CAR. The initial single-center phase 1-2a study The advent of chimeric antigen receptors has demonstrated promising results in RR-ALL. the data demonstrate that CD19-targeted CAR T cells can induce prolonged remissions in patients with B cell malignancies, often with minimal long-term toxicities, and are Although anti-CD20 mAb therapy depleted B cells in the CNS and the periphery in this mouse model, it is known that anti-CD20 mAbs do not penetrate the CNS well in humans, 6-8 whereas anti-CD19 CAR-T cells do. Clinical trials demonstrated that CD19+ chimeric antigen receptor (CAR) T-cells can be highly effective against a number of malignancies. CD19 is a cell surface protein that is generally restricted to B cells and their precursors and is expressed by most B cell malignancies [68, 69]. CD19-targeted chimeric antigen receptor (CAR) T-cell therapy, originally developed for B-cell malignancies, has shown promising efficacy in B-cell-driven autoimmune diseases such as systemic lupus erythematosus (SLE), systemic sclerosis, and myasthenia gravis. In this strategy, a patient's own T cells are genetically engineered to express a synthetic receptor that binds a tumor antigen. Adoptive transfer of autologous CD19-targeted CAR-T cells has become the first genetically modified cell-based therapy approved by the U. T cell persistence, lymphodepletion regimen, CD3/CD28 beads treatment and no IL-2 administration to T cells were positively associated with better responses. Anti-CD19 CAR-T-cell cannot kill B-cells with hemizygous deletions spanning CD19-targeted chimeric antigen receptors (CAR) T cells are one of the most remarkable cellular therapies for managing B cell malignancies. 15 The main components of a CAR system are the CD3 zeta intracellular domain of the T-cell receptor, the transmembrane domain, the hinge, and a single-chain variable fragment (scFv). Furthermore, many other institutions reported similar results, which led to the US approval of the CD19 CAR T-cell therapy in 2017 by the FDA. Commercial anti-CD19 CAR T cell therapy for patients with relapsed/refractory aggressive B cell lymphoma in a European center. Previous article in issue; Next article in issue; (FDA) approved CD19-CAR-T-cell therapy in 2017 for the treatment of a subset of pediatric and young adult patients with acute lymphoblastic leukemia, and since then, Mutations in CD19 which result in CD19-antigen loss are common in CD19-negative relapse after CD19 CAR-T-cell therapy. 1,2 However, despite initial remission rates of greater than 80% across studies, durable remission Objectives: This study evaluated the benefits and risks of patients with refractory or relapsed acute lymphocytic leukemia (R/R ALL) treated with anti-CD19 chimeric antigen receptor (CAR) T-cell therapy and blinatumomab. Further, CRISPR-based Chimeric antigen receptor (CAR)-T cell therapy is a promising new treatment for cancer that involves genetically modifying a patient’s T-cells to recognize and attack cancer cells. Therefore, rather than using CAR-T cell therapy as a stand-alone option, consolidation with allogeneic stem-cell transplant (Allo-SCT) after CAR-T treatment might increase long-term outcome. 40 In a first-in-human study (NCT04684563) testing CD19-CAR–IL-18 in adult patients with B-cell malignancies (including those who did not respond to earlier CAR T-cell therapies) CAR T cells were manufactured in only 3 days . 8 years) 18,42–53 Abstract CD19-directed autologous chimeric antigen receptor T cell (CAR-T) therapy has transformed the management of relapsed/refractory (R/R) large B cell lymphoma (LBCL). CD19 chimeric antigen receptor (CAR) T cell therapy has shown impressive results in treating acute lymphoblastic leukemia (B-ALL), chronic lymphoblastic leukemia (B-CLL), and B-cell non-Hodgkin lymphoma (B-NHL) over the past few years. When CD19 CAR-T cells recognize normal or malignant CD19+ cells in the patient, signaling through the CAR induces CAR-T cell proliferation, cytokine production, and lysis of target cells . 4 Another trial, NCT02706405, indicated that initiating anti-PD-L1 antibody Chimeric antigen receptor T (CAR-T) cell therapy is an effective treatment for relapsed or refractory diffuse large B cell lymphoma (DLBCL) with 3 CD19 targeting products now FDA-approved for this indication. Clinical administration of anti-CD19 CAR T-cells resulted in accumulation of vast CD19-redirected chimeric antigen receptor (CAR) T-cell therapy is an effective therapeutic modality for pediatric patients with relapsed and/or refractory (R/R) acute lymphoblastic leukemia (B-ALL), a patient cohort that historically was largely incurable. NCT02650999, for instance, explored pembrolizumab in B cell lymphomas that were unresponsive to or that relapsed after CD19-CAR T cell therapy, with 4 out of 12 patients experiencing clinical benefit, including a boosting of CAR T cell frequencies in peripheral blood. The purpose of the s Allogeneic anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has the potential for extensive clinical applications. CAR T-cells are autologous T-cells transduced with a chimeric antigen receptor which targets the modified T-cell against a specified cancer antigen. 4 Another trial, NCT02706405, indicated that initiating anti-PD-L1 antibody In this review, we summarize the mechanisms through which CAR-T cells are used to target autoimmune conditions, including the targeting of autoreactive B cells and T cells, as well as the engineering of regulatory T cells. Efficacy of CAR-T cell therapy. Clinical studies report suboptimal outcomes such as reduced cytotoxicity of CAR-T cells and tumor evasion, underscoring the need to address the challenges of sliding cytotoxicity in CAR-T Chimeric antigen receptor T (CAR-T) cell therapy is an effective treatment for relapsed or refractory diffuse large B cell lymphoma (DLBCL) with 3 CD19 targeting products now FDA-approved for this indication. They find that in this advance toward a new CD19-targeted CAR T cell therapy for B-ALL. At the dawn of this decade, the first successful use of CAR T cell therapy to treat B cell malignancies were published (2–4). 2. Toxicities of CAR-T cell therapy. Adoptive T cell therapy is a prominent therapeutic method that demands precise T cell editing and signal regulation. Chimeric antigen receptor T (CAR-T) cell therapy has succeeded dramatically in treating hematological malignancies. Herein, we discuss the factors that can preclude durable remissions Anti-CD19 chimeric antigen receptor (CAR) T-cell therapies can be effective treatments for patients with r/r DLBCL. Chimeric antigen receptor (CAR) T-cell therapy has had a substantial effect on the treatment landscape of advanced B-cell cancers. In this review, we summarized the critical factors for better efficacy of CD19 CAR-T cells in B-lineage malignancies including B-ALL, B-CLL and lymphoma. CAR-T cell therapy can be associated with significant toxicities that occur as a result of T cell activation and other The approval of CD19-directed chimeric antigen receptor (CAR) T-cell therapies for the second-line treatment of high-risk large B-cell lymphoma (LBCL) has greatly affected salvage algorithms for this condition, and such therapies could have the Sesques P, Ferrant E, Safar V, et al. In parallel, synergistic therapeutic combinations are being developed to potentiate CAR-T cell cytotoxicity and in vivo persistence 6. CAR T cells are This review addresses T-cell engineering and synthetic immunity, with a focus on producing durable remissions in patients with treatment-refractory tumors. Here we generated a new anti Failure of ALL recognition by CAR T cells: a review of CD 19-negative relapses after anti-CD 19 CAR-T treatment in B-ALL 2 Maimonides Institute of Biomedical Research in Cordoba (IMIBIC), Cell Therapy, Cordoba, Spain. Various anti-CD19 CAR T-cell constructs have been trialled and responses vary widely among different studies. This review provides an overview of the latest discoveries and clinical trials related to CAR-T cell therapy, as well as the concept and applications of the therapy. Alternative immune cells, The review concludes that CD20-targeted chimeric antigen receptor (CAR) T-cell therapy is an option worth exploring, despite potential safety concerns that warrant more extensive research. We aimed to systematically analyse the outcomes of patients with acute lymphocytic leukaemia Background: CD22 single and CD19/CD22 bispecific targeted chimeric antigen receptor T (CAR-T) cell therapy are promising immunotherapy modalities for the treatment of hematologic malignancies. Preliminary data for such humanized anti Chimeric antigen receptor (CAR) T-cell therapy has shown promise for relapsed/refractory malignancies. We here conducted a meta-analysis to confirm its efficacy and safety. Anti-CD19 chimeric antigen receptors (CARs) are artificial fusion proteins that cause CD19-specific T-cell activation. S. Phase 1 results of ZUMA-1: A multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Four databases w CD19-targeting chimeric antigen receptor (CAR) T-cell therapy has shown remarkable outcomes in patients with systemic lupus erythematosus. Although anti-CD19 CAR-T cell therapy and anti-BCMA CAR-T cell therapy have achieved outstanding outcomes in B cell malignancies, relapse after CAR-T Chimeric antigen receptor T (CAR-T) cell therapy is an effective treatment for relapsed or refractory diffuse large B cell lymphoma (DLBCL) with 3 CD19 targeting products now FDA-approved for this indication. Clinical trials targeting CD19, other hematologic and solid malignancies. Despite advancements in understanding response mechanisms, resistance patterns, and adverse events associated with CAR T-cell therapy, the translation of these insights into Chimeric antigen receptor (CAR) T cells have demonstrated impressive success in the treatment of some cancers. 1 The first-generation CAR molecule consists of a single-chain variable In preclinical models, engineered IL-18 conferred superior anti-tumour activity and CAR T-cell proliferation in vivo. We review novel strategies and sophisticated CAR designs that may overcome these barriers. In October 2017, the FDA approved the world’s second CAR-T cell therapy—Yescarta. CAR T cell therapy. doi: 10. The review also discusses the In April 2012, following successes first experienced with CD19-directed chimeric antigen receptor (CAR) T cell therapy in adults with follicular lymphoma or chronic lymphocytic leukaemia (CLL) 1,2 PURPOSE. 27% of all In this review, we will discuss some recent developments in the field of breast cancer-specific immunotherapy using CAR-T. Based on clinicaltrial. Single-targeting CD19 CAR-T cells. For example, in a clinical trial testing CD19-targeting CAR-T cell therapy in the treatment of refractory large B cell In an in vivo model of primary B-ALL, injection of 4-1BB-CD3ζ CD19-targeted CAR T cells resulted in improved survival of T cells compared to CD28-CD3ζ CD19-targeted CAR T cells . When re-infused into the patient, the CAR T-cells bind to the antigen Chimeric Antigen Receptor (CAR)-T cell therapy is an exciting development in the field of cancer immunology, wherein immune T-cells from patients are collected, engineered to create ‘CAR’-T cells, and infused back into the same patient. Safety and efficacy outcomes from the pivotal prospective clinical trials of axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel and the retrospective, The resistance to CAR-T therapy caused by CAR-T cell exhaustion has prompted the dissection of CAR-T cell clonotype and functional state at high resolution by single-cell sequencing technologies 5. The most widely used approaches include CD19/CD20, CD20/CD22, and BCMA/CD19 CAR T-cells. 8 million km 2. Tisagenlecleucel and brexucabtagene autoleucel are anti-CD19 CAR-T (CART-19) cell therapies approved for the treatment of relapsed/refractory (rel/ref) ALL [19, 20]. Here we review state-of-the-art clinical data on CD19-directed CAR T cell therapies in B cell hematologic malignancies, advances made in understanding and modeling associated toxicities, and several exciting advances and creative solutions for overcoming challenges with this therapeutic modality. It may also help overcome limitations of currently approved CAR‐T‐cell therapies. Background: Several chimeric antigen receptor T cells (CAR T) targeting CD19 have induced profound and prolonged remission for refractory/relapsed (R/R) B-cell lymphoma. In addition, although the ability to re-treat patients could ultimately be beneficial, the treatment regimens in the trial above involved multiple outpatient infusions, which add an additional NCT02650999, for instance, explored pembrolizumab in B cell lymphomas that were unresponsive to or that relapsed after CD19-CAR T cell therapy, with 4 out of 12 patients experiencing clinical benefit, including a boosting of CAR T cell frequencies in peripheral blood. 75 and 0. The overall complete response rates of CD22 and CD19/CD22 NCT02650999, for instance, explored pembrolizumab in B cell lymphomas that were unresponsive to or that relapsed after CD19-CAR T cell therapy, with 4 out of 12 patients experiencing clinical benefit, including a boosting of CAR T cell frequencies in peripheral blood. In this systematic This review discusses the potential of CD19 CAR-T cells in ARDs, highlighting clinical achievements and addressing key considerations such as optimal target cell C D19-directed chimeric antigen receptor (CAR) T-cell therapy, originally developed for haematological malignancies, has recently emerged as a promising therapy for In this Review, we provide guidance for a rational management approach to the use of commercial CD19-directed CAR T cells in the second-line treatment of LBCL, addressing In the past few years, CD19-based and B cell maturation antigen (BCMA)-based CAR T cell therapies have been applied to various B cell-mediated autoimmune diseases One of the current most effective CAR T cell therapies targets CD19, an antigen expressed by B cells in all stages of development until differentiation in plasmocytes, including Recent experience suggests that CD19-CAR T-cell therapy represents a potentially transformative new therapy approach achieving lasting, treatment-free remission in autoimmune diseases. In the beginning of CD19-CAR-T cell therapy, it was observed that patients with a higher leukemia burden would facilitate a better engraftment of CD19-CAR-T cells and thus CAR T cell therapy would be more successful. This is the first reported use of CD19 CAR T cell product in IMNM. This review will briefly summarize the current data supporting the use of adoptively transferred CAR T cells for the treatment of CD19-positive malignancies. We review available evidence regarding safety and feasibility of outpatient administration of CD19 targeted and BCMA targeted CAR T-cell therapy with an emphasis on the implementation of outpatient CAR-T programs in community-based centers. This therapy is promising, as demonstrated in several clinical trials []. Naoki Hosen Department of Hematology and Oncology, Osaka University cell injection. Chimeric antigen receptor-modified T cells (CAR-T) and engineered T cells are used to target cancer cells. C D19-directed chimeric antigen receptor (CAR) T-cell therapy, originally developed for haematological malignancies, has recently emerged as a promising therapy for patients with autoimmune diseases. In this article, we have conducted a thorough review of the history and development of CAR-T cell therapy and outlined its high efficacy in the field of acute leukemia. Chimeric antigen receptor (CAR) T cell therapy improves the remission rate of refractory/relapsed B-acute lymphoblastic leukemia (R/R B-ALL) patients, but the relapse rate remains high. Methods: PubMed, Web of Science, Embase, and the Cochrane Library were searched for relevant studies. However, long-term disease-free survival is still a challenge to overcome. Heery C, Shah B. Durability of remissions and incidence of long-term adverse events are critical factors determining the utility of anti-CD19 CAR T-cell therapy, but long-term follow-up of patients treated with anti-CD19 CAR T cells is limited. Our institution is the sole provider of CAR T-cell therapy in Queensland and northern Australia; servicing a population of approximately 6 million people over 3. Recent studies suggest patients who underwent post-chimeric antigen receptor T cell therapy hematopoietic stem cell transplantation (post- HSCT) would achieve durable The approval of CD19-directed chimeric antigen receptor (CAR) T-cell therapies for the second-line treatment of high-risk large B-cell lymphoma (LBCL) has greatly affected salvage algorithms for this condition, and such therapies could have the potential to improve the course of relapsed or refractory LBCL. Short-term complications such as cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS), have been well reported Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment for relapsed/refractory B-cell lymphomas. Mutations in CD19 which result in CD19-antigen loss are common in CD19-negative relapse after CD19 CAR-T-cell therapy. This systematic review and meta-analysis showed that pooled complete remission for patients with B-cell acute lymphocytic leukaemia who were treated with anti-CD19 CAR T-cell therapy was 80% (95% CI 75·5–84·8), the pooled 1 In a clinical study performed on 13 children (ranging in age from 4 to 17 years) with relapsed or refractory B-cell ALL treated with CD19-directed CAR T-cell therapy, it was observed that PD-1 CART-19 in ALL. Remarkable response rates and prolonged remissions have been achieved in this setting, leading to regulatory approval from the U. CD19-targeted CAR-T cell therapy has been utilized, but the risks and benefits are unknown. [PMC The overall complete response rates of CD22 and CD19/CD22 CAR-T cell therapies for relapsed or refractory B-ALL were 0. However, up to 60% of patients ultimately progress or relapse following CAR-T cell therapy. Food and Drug Administration (FDA) of four CAR T cell The success of chimeric antigen receptor (CAR) T cell therapy has been hindered by barriers intrinsic to the tumor microenvironment, including metabolic fuel competition, physical barriers to effective CAR T cell infiltration, and immunosuppressive cytokines and cell types. Meanwhile, the cytokine release syndrome (CRS), which could be moderate or even life-threatening, has emerged as Currently, CD19 and BCMA are the most common targets in CAR-T cell therapy. Chimeric antigen receptor (CAR) T cell therapy stands as a transformative advancement in immunotherapy, triumphing against hematological malignancies and, increasingly, autoimmune disorders. [PMC Cryopreservation of CAR T cell therapy products is necessary for expanding production and access to CAR T therapies; however, there have been mixed data on the effect of cryopreservation on CAR T cell function. Many patients have undergone prior hematopoietic stem cell transplant (HSCT), yet effects of transplant status on CAR T-cell therapy efficacy and safety have not been reported. of CD19 CAR T cells for relapsed and CD19 is thought to be the first antigen targeted by CAR T-cell therapy to cure relapsed/refractory nonhodgkin lymphoma (r/r NHL) with large B-cell lymphoma (LBCL) as their predominant type. In this review, we described the research and development status of universal CAR-T therapy for hematological malignancies. Adverse effects in hematologic malignancies treated with chimeric antigen receptor (CAR) T cell therapy: a systematic review and meta-analysis. gov (March 2021): 41% of worldwide clinical trials aim at CD19 CAR T cells. Methods: Review and compilation of the most recent and relevant data published in full text and abstract forms of anti-CD19 CAR T-cell therapy for B-cell NHL. The second-generation CAR T cell therapy demonstrated effectiveness in one patient with advanced follicular lymphoma at NCI (), and in patients with refractory CLL and relapsed B-cell ALL at MSKCC (). ’s meta-analysis. Consolidative Hematopoietic Stem Cell Transplantation After CD19 CAR-T Cell Therapy for Acute Lymphoblastic Leukemia: A Systematic Review and Meta Summary of clinical trials targeting CAR T cells. 4 The clinical success of CAR T cell therapy. Given these exciting results, the Food and Drug Administration has granted a 'breakthrough' designation for several variations of CD19-directed CAR T cells for treatment of adult and Background: Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable activity in patients with refractory or relapsed acute lymphocytic leukaemia. 1-3 The vast majority of NHLs are derived from B cells. The more than 80 subtypes of B-cell NHL are categorized according to their typical clinical course: indolent or aggressive. Correspondingly, one of the research articles authored by Liu et al. Mol. Chimeric antigen receptor (CAR) T-cell therapy is novel immunotherapy, targeting specifically cancerous cells, and inducing durable remissions in some refractory hematological malignancies like multiple myeloma (MM) []. Currently, there is emerging evidence derived from post approval studies in CD19+ CAR T-cells demonstrating both short-term and medium Aim: Chimeric antigen receptor T cell (CAR-T) therapies targeting CD19 have transformed treatment of relapsed/refractory large B cell lymphoma and B cell leukaemia (B-ALL). 4 Aggressive B-cell NHLs that are Chimeric antigen receptor (CAR) T-cell therapies that specifically target the CD19 antigen have emerged as a highly effective treatment option in patients with refractory B-cell hematological malignancies. 2022;22(1):98. New CAR T-cell therapies in development aim to Chimeric antigen receptor (CAR) T cells directed against the B cell antigens CD19 and B cell maturation antigen (BCMA) are a potent immunotherapy for multiple advanced B cell malignancies and are P: participants (RRMM patients), I: interventions (combined anti-BCMA and anti-CD19 CAR-T cell therapy), C: comparisons (this analysis included single-arm studies without a control group), O: outcomes (the outcome was the efficacy and safety of combined anti-BCMA and anti-CD19 CAR-T cell therapy), S: study designs (Phase I and II clinical Chimeric antigen receptor (CAR) T-cell therapy presents a promising approach for treating certain types of hematological malignancies. Some off-target effects such as B cell aplasia after CD19 CAR-T cell therapy may occur, and this may predispose to infection and Buchholz and colleagues review recent publications providing preclinical proof of concept for the generation of CAR T cells directly in vivo. In 2017, the US Food and Drug Administration approved CD19-specific CAR-T (tisagenlecleucel) therapy for RR-B-cell ALL in patients under 25 years old. The median persistence of CAR T cells in blood was 28 d after the first CAR T cell infusion, and responders displayed modestly higher peak CAR T cell counts than nonresponders (5,638 versus 4,131 The findings of this review indicate that CAR-T cell therapies represent a powerful and effective anti-cancer treatment modality, albeit with an effect that is both variable and limited to specific diseases. Universal CAR-T therapy could overcome major limitations of autologous CAR-T therapy. However, its application in solid tumors is still limited. CAR T-cell therapy involves the genetic modification of a patient’s autologous T-cells to express a chimeric antigen receptor specific for a tumour antigen . Despite its success, this therapy is accompanied by a significant frequency of adverse events, including cytokine release syndrome (CRS), immune-effector-cell-associated neurotoxicity syndrome (ICANS), or cytopenias, reaching even up to Background: Several chimeric antigen receptor T cells (CAR T) targeting CD19 have induced profound and prolonged remission for refractory/relapsed (R/R) B-cell lymphoma. Nevertheless, several clinical trials have started investigating the safety and efficacy of CD19-BCMA CAR-T cell infusion in various autoimmune conditions . 14 Once bound Background CD19-targeted chimeric antigen receptor T (CAR-T) cell therapy stands out as a revolutionary intervention, exhibiting remarkable remission rates in patients with refractory/relapsed (R/R) B-cell malignancies. Meanwhile, the cytokine release syndrome (CRS), which could be m The present review presents an insight into the advantages and the advances of CAR immunotherapy and presents the emerging discrepancy of CAR therapy over usual forms of therapy, such 3. CD19 CAR T cells induced a rapid and sustained depletion of circulating B cells, as well as in a complete clinical and serological remission of refractory systemic lupus erythematosus and dermatomyositis. We report the first case of diffuse large B-cell lymphoma (DLBCL) PTLD treated with lisocabtagene maraleucel and present a systematic literature review of SOTRs with PTLD treated with CD19 CAR-T therapy. Recent clinical trials have demonstrated that engineered T cells are highly active tumor effector cells. such as acquired mutations and alternative splicing of the CD19 antigen, CD19 epitope loss or masking, leukemia lineage The combined anti-BCMA and anti-CD19 CAR-T cell therapy showed high clinical efficacy in several clinical trials for RRMM. Review Article. 14 Once bound Furthermore, the initial experience with CAR T cells has highlighted challenges associated with manufacturing a patient-specific therapy. In this Sesques P, Ferrant E, Safar V, et al. The risk of secondary malignancies, especially myeloid neoplasms, is of particular concern in the CAR T community, which still remains unclear. (CD19/CD7) CAR-T cell therapy developed based on the TruUCAR platform from Gracell Biotechnologies, is in the Phase I clinical trial CAR-T (chimeric antigen receptor T) cell therapies employ an individual’s own genetically engineered T cells to combat malignancies 1 and have demonstrated success in patients suffering from chemorefractory B cell 1 Introduction. This process involves ex vivo expansion of tumor-specific T cells followed by their reintroduction into patients to swiftly restore host immunity (). Shah In this review, we discuss the mechanisms by which CAR-T cells target autoimmune conditions, summarize current preclinical models, and highlight ongoing clinical trials, including CAR-T therapy design, clinical outcomes, and challenges. However, the emergence of cytokine release syndrome (CRS) as a side effect poses a challenge to the widespread application of CAR-T cell therapies. CD19-targeted CAR T cells are now approved for relapsed and/or refractory B cell lymphoma and B cell acute lymphoblastic leukaemia, and B cell maturation antigen-targeted CAR T cells are We evaluated 15 patients with severe SLE (8 patients), idiopathic inflammatory myositis (3 patients), or systemic sclerosis (4 patients) who received a single infusion of CD19 In 2017, the US Food and Drug Administration approved CD19-specific CAR-T (tisagenlecleucel) therapy for RR–B-cell ALL in patients under 25 years old. The present review presents an insight into the advantages and the advances of CAR immunotherapy and presents the emerging discrepancy of CAR therapy over usual forms of therapy, such as chemotherapy and radiotherapy. CD19/BCMA CAR-T cell therapy for refractory systemic lupus erythematosus - safety and preliminary Abstract: Non-Hodgkin lymphoma (NHL) is the seventh most common type of malignancy worldwide, with approximately 544,000 cases diagnosed in 2020. The aim of this study was to assess the efficacy and safety of CD22 and CD19/CD22 targeted CAR-T cell therapy by summarizing the existing evidence. Chimeric antigen receptor (CAR)-T cell therapy demonstrates substantial efficacy in various hematological malignancies. [Skip to Navigation] CAR T-cell therapy is associated with reversible acute toxicities, such as cytokine release syndrome in approximately 40% to 95% of patients, and neurologic disorders in approximately 15% to 65%. 2021 Apr;100(4):1003-1012. Moreover, CD19 is one target, but several other targets are being examined, such as CD20 and CD22 and dual-targeting CARs or combination therapy. njkjykx wnbqx antz nbakv lvwgv xylptj miydyr etz qfpapy wtehwx